Non-compressible truncal and junctional hemorrhage: A retrospective analysis quantifying potential indications for advanced bleeding control in Dutch trauma centers.

BACKGROUND: Truncal and junctional hemorrhage is the leading cause of potentially preventable deaths in trauma patients. To reduce this mortality, the application of advanced bleeding control techniques, such as resuscitative endovascular balloon occlusion of the aorta (REBOA), junctional tourniquets, Foley catheters, or hemostatic agents should be optimized. This study aimed to identify trauma patients with non-compressible truncal and junctional hemorrhage (NCTJH) who might benefit from advanced bleeding control techniques during initial trauma care. We hypothesized that there is a substantial cohort of Dutch trauma patients that can possibly benefit from advanced bleeding control techniques. METHODS: Adult trauma patients with an Abbreviated Injury Scale ≥3 in the torso, neck, axilla, or groin region, who were presented between January 1st, 2014 and December 31st, 2018 to two Dutch level-1 trauma centers, were identified from the Dutch Trauma Registry. Potential indications for advanced bleeding control in patients with NCTJH were assessed by an expert panel of three trauma surgeons based on injury characteristics, vital signs, response to resuscitation, and received treatment. RESULTS: In total, 1719 patients were identified of whom 249 (14.5 %) suffered from NCTJH. In 153 patients (60.6 %), hemorrhagic shock could have been mitigated or prevented with advanced bleeding control techniques. This group was younger and more heavily injured: median age of 40 versus 48 years and median ISS 33 versus 22 as compared to the entire cohort. The mortality rate in these patients was 31.8 %. On average, each of the included level-1 trauma centers treated an NCTJH patient every 24 days in whom a form of advanced bleeding control could have been beneficial. CONCLUSIONS: More than half of included Dutch trauma patients with NCTJH may benefit from in-hospital application of advanced bleeding control techniques, such as REBOA, during initial trauma care. Widespread implementation of these techniques in the Dutch trauma system may contribute to reduction of mortality and morbidity from non-compressible truncal and junctional hemorrhage.

Early Femoral Access by Acute Care Surgeons: A Multidisciplinary Approach to Prevent Maternal Exsanguination in Placenta Accreta Spectrum.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) use has expanded to the obstetric condition of placenta accreta spectrum (PAS). Early reports of REBOA for PAS describe prophylactic catheter deployment. We developed a multidisciplinary approach to PAS, with early femoral artery access and selective REBOA deployment. We compared morbidity, mortality, and blood loss before and after implementation of our multidisciplinary protocol for PAS. Prior to, femoral access was obtained only emergently, and maternal death occurred in 2/3 cases (66%). Following protocol implementation, there was one maternal death (6%). There were no access-related complications. We have not yet needed to deploy the REBOA during PAS cases. In contrast to urgent hemorrhage control or prophylactic REBOA deployment, routine early femoral arterial access and selective REBOA deployment as part of a multidisciplinary team approach is a novel strategy for managing PAS. Our experience suggests most PAS cases do not require prophylactic REBOA deployment.

Guideline nº 431: postpartum hemorrhage and hemorrhagic shock

This guideline aims to provide evidence for prevention, recognition, and treatment of postpartum hemorrhage including severe hemorrhage leading to hemorrhagic shock. Benefits, harms, and costs Appropriate recognition and treatment of postpartum hemorrhage can prevent serious morbidity while reducing costs to the health care system by minimizing more costly interventions and length of hospital stays. Medical literature, PubMed, ClinicalTrials.gov, the Cochrane Database, and grey literature were searched for articles, published between 2012 and 2021, on postpartum hemorrhage, uterotonics, obstetrical hemorrhage, and massive hemorrhage protocols. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). All members of the health care team who care for labouring or postpartum women, including, but not restricted to, nurses, midwives, family physicians, obstetricians, and anesthesiologists.

Phosphoinositide-3-Kinase/Akt-Endothelial Nitric Oxide Synthase Signaling Pathway Mediates the Neuroprotective Effect of Sevoflurane Postconditioning in a Rat Model of Hemorrhagic Shock and Resuscitation.

BACKGROUND: Although extensive reports have demonstrated the neuroprotection of sevoflurane postconditioning in cases of focal and global cerebral ischemia/reperfusion, the underlying mechanisms are not completely elucidated. This study investigated whether this effect is related to endothelial nitric oxide synthase (eNOS) and mediated by the phosphoinositide-3-kinase pathway in a rat model of hemorrhagic shock and resuscitation. METHODS: Adult male Sprague Dawley rats were subjected to hemorrhagic shock for 60 minutes and then resuscitation for 30 minutes in experimental groups. Sevoflurane postconditioning was performed at the beginning of resuscitation to completion. At 24 hours after resuscitation, the brain infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining. The neuronal morphological changes and apoptosis were determined by hematoxylin and eosin staining and immunohistochemistry analysis, respectively. The activity of phosphorylated Akt and eNOS was evaluated by Western blot analysis. RESULTS: Brain injuries such as the cerebral infarct volume and pathological neuronal changes as well as cell apoptosis were observed in the hippocampus after hemorrhagic shock and resuscitation. Postconditioning with 2.4% sevoflurane significantly attenuated brain injuries. Wortmannin prevented the improvements of neuronal characteristics elicited by sevoflurane postconditioning as well as the hyperactivity of eNOS and phosphorylated Akt. CONCLUSIONS: Sevoflurane postconditioning could attenuate brain injury induced by hemorrhagic shock and resuscitation, and this neuroprotective effect may be partly by upregulation of eNOS through the phosphoinositide-3-kinase/Akt signaling pathway.

Patterns and outcomes of zone 3 REBOA use in the management of severe pelvic fractures: Results from the AAST Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery database.

BACKGROUND: Knowledge on practice patterns for aortic occlusion (AO) in the setting of severe pelvic fractures is limited. This study aimed to describe clinical outcomes based on number and types of interventions after zone 3 resuscitative endovascular balloon occlusion of the aorta (REBOA) deployment. METHODS: A retrospective review of the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery multicenter registry was performed for patients who underwent zone 3 AO from 2013 to 2020. Patients with a blunt mechanism who survived beyond the emergency department were included. Interventions evaluated were preperitoneal pelvic packing (PP), angioembolization (AE), and external fixation (EF) of the pelvis. Management approaches were compared against the primary outcome of mortality. Secondary outcomes included transfusion requirements, overall complications and acute kidney injury (AKI). RESULTS: Of 207 patients who underwent zone 3 AO, 160 (77.3%) fit the inclusion criteria. Sixty (37.5%) underwent AO alone, 50 (31.3%) underwent a second hemostatic intervention, and 49 (30.6%) underwent a third hemostatic intervention. Overall mortality was 37.7% (n = 60). There were no differences in mortality based on any number or combination of interventions. On multivariable regression, only EF was associated with a mortality reduction (odds ratio, 0.22; p = 0.011). Increasing number of interventions were associated with higher transfusion and complication rates. Pelvic packing + AE was associated with increased AKI than PP or AE alone (73.3% vs. 29.5% and 28.6%, p = 0.005), and AE was associated with increased AKI resulting in dialysis than PP alone (17.9% vs. 6.8%, p = 0.036). CONCLUSION: Zone 3 REBOA can be used as a standalone hemorrhage control technique and as an adjunct in the management of severe pelvic fractures. The only additional intervention associated with a mortality reduction was EF. The benefit of increasing number of interventions must be weighed against more harm. Heterogeneity in practice patterns for REBOA use in pelvic fracture management underscores the need for an evidence base to standardize care. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Targeting Uric Acid Prevents Brain Injury and Anxiety in a Rat Model of Hemorrhagic Shock.

ABSTRACT: Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS. Since UA is implicated in endothelial dysfunction and inflammatory response, we hypothesized UA could alter the blood-brain barrier (BBB) and impact the brain. Male Wistar rats were randomly assigned to: SHAM, HS (hemorrhagic shock) and HS + U (hemorrhagic shock + 1.5 mg/kg of uricase). The uricase intervention, specifically targeting UA, was administered during fluid resuscitation. It prevented BBB dysfunction (fluorescein sodium salt permeability and expression of intercellular adhesion molecule-1) following HS. As for neuroinflammation, all of the results obtained (MPO activity; Iba1 and GFAP expression) showed a significant increase after HS, also prevented by the uricase. The same pattern was observed after quantification of apoptosis (caspase-3 activity and TUNEL) and neurodegeneration (Fluoro-Jade). Finally, the forced swim, elevated plus maze, and social interaction tests detected anxiety-like behavior after HS, which was blunted in rats treated with the uricase. In conclusion, we have identified UA as a new circulatory inflammatory mediator, responsible for brain alterations and anxious behavior after HS in a murine model. The ability to target UA holds the potential of an adjunctive therapeutic solution to reduce brain dysfunction related to hemorrhagic shock in human.

Intra-abdominal Inferior Vena Cava Injuries: Operative Strategies and Outcomes.

Visceral vascular injuries are relatively uncommon even in busy urban trauma centers. The inferior vena cava (IVC) is the most frequently injured visceral vein and can be a complex operative challenge. Despite advances in early volume resuscitation, improved transport times, prompt operative intervention, and hemorrhage control, mortality rates have remained largely unchanged. This article conducts an in-depth review of the literature surrounding IVC injuries and a detailed discussion of operative strategies and management as survivability is ultimately dependent on the grade of injury, location, and the presence of hemorrhagic shock.

Modulation of Brain Transcriptome by Combined Histone Deacetylase Inhibition and Plasma Treatment Following Traumatic Brain Injury and Hemorrhagic Shock.

INTRODUCTION: We previously showed that the addition of valproic acid (VPA), a histone deacetylase inhibitor, to fresh frozen plasma (FFP) resuscitation attenuates brain lesion size and swelling following traumatic brain injury (TBI) and hemorrhagic shock (HS). The goal of this study was to use computational biology tools to investigate the effects of FFP+VPA on the brain transcriptome following TBI+HS. METHODS: Swine underwent TBI+HS, kept in shock for 2 h, and resuscitated with FFP or FFP + VPA (n = 5/group). After 6 h of observation, brain RNA was isolated and gene expression was analyzed using a microarray. iPathwayGuide, Gene Ontology (GO), Gene-Set Enrichment Analysis, and Enrichment Mapping were used to identify significantly impacted genes and transcriptomic networks. RESULTS: Eight hundred differentially expressed (DE) genes were identified out of a total of 9,118 genes. Upregulated genes were involved in promotion of cell division, proliferation, and survival, while downregulated genes were involved in autophagy, cell motility, neurodegenerative diseases, tumor suppression, and cell cycle arrest. Seven hundred ninety-one GO terms were significantly enriched. A few major transcription factors, such as TP53, NFKB3, and NEUROD1, were responsible for modulating hundreds of other DE genes. Network analysis revealed attenuation of interconnected genes involved in inflammation and tumor suppression, and an upregulation of those involved in cell proliferation and differentiation. CONCLUSION: Overall, these results suggest that VPA treatment creates an environment that favors production of new neurons, removal of damaged cells, and attenuation of inflammation, which could explain its previously observed neuroprotective effects.

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials.

OBJECTIVE: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia. BACKGROUND: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators. METHODS: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability. CONCLUSIONS: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

The Critical Choice of Animal Models in Nanomedicine Safety Assessment: A Lesson Learned From Hemoglobin-Based Oxygen Carriers.

Intravenous injection of nanopharmaceuticals can induce severe hypersensitivity reactions (HSRs) resulting in anaphylactoid shock in a small percentage of patients, a phenomenon explicitly reproducible in pigs. However, there is a debate in the literature on whether the pig model of HSRs can be used as a safety test for the prediction of severe adverse reactions in humans. Given the importance of using appropriate animal models for toxicity/safety testing, the choice of the right species and model is a critical decision. In order to facilitate the decision process and to expand the relevant information regarding the pig or no pig dilemma, this review examines an ill-fated clinical development program conducted by Baxter Corporation in the United States 24 years ago, when HemeAssist, an αα (diaspirin) crosslinked hemoglobin-based O2 carrier (HBOC) was tested in trauma patients. The study showed increased mortality in the treatment group relative to controls and had to be stopped. This disappointing result had far-reaching consequences and contributed to the setback in blood substitute research ever since. Importantly, the increased mortality of trauma patients was predicted in pig experiments conducted by US Army scientists, yet they were considered irrelevant to humans. Here we draw attention to that the underlying cause of hemoglobin-induced aggravation of hemorrhagic shock and severe HSRs have a common pathomechanism: cardiovascular distress due to vasoconstrictive effects of hemoglobin (Hb) and reactogenic nanomedicines, manifested, among others, in pulmonary hypertension. The main difference is that in the case of Hb this effect is due to NO-binding, while nanomedicines can trigger the release of proinflammatory mediators. Because of the higher sensitivity of cloven-hoof animals to this kind of cardiopulmonary distress compared to rodents, these reactions can be better reproduced in pigs than in murine or rat models. When deciding on the battery of tests and the appropriate models to identify the potential hazard for nanomedicine-induced severe HSR, the pros and cons of the various species must be considered carefully.

Association of Prehospital Plasma With Survival in Patients With Traumatic Brain Injury: A Secondary Analysis of the PAMPer Cluster Randomized Clinical Trial.

Importance: Prehospital plasma administration improves survival in injured patients at risk for hemorrhagic shock and transported by air ambulance. Traumatic brain injury (TBI) is a leading cause of death following trauma, but few early interventions improve outcomes. Objective: To assess the association between prehospital plasma and survival in patients with TBI. Design, Setting, and Participants: The Prehospital Air Medical Plasma (PAMPer) trial was a pragmatic, multicenter, phase 3, cluster randomized clinical trial involving injured patients who were at risk for hemorrhagic shock during air medical transport to a trauma center. The trial was conducted at 6 US sites with 9 level-I trauma centers (comprising 27 helicopter emergency services bases). The original trial analyzed 501 patients, including 230 patients who were randomized to receive plasma and 271 randomized to standard care resuscitation. This secondary analysis of a predefined subgroup included patients with TBI. Data analysis was performed from October 2019 to February 2020. Interventions: Patients were randomized to receive standard care fluid resuscitation or 2 units of thawed plasma. Main Outcomes and Measures: The primary outcome was mortality at 30 days. Patients with TBI were prespecified as a subgroup for secondary analysis and for measurement of markers of brain injury. The 30-day survival benefit of prehospital plasma in subgroups with and without TBI as diagnosed by computed tomography was characterized using Kaplan-Meier survival analysis and Cox proportional hazard regression. Results: In total, 166 patients had TBI (median [interquartile range] age, 43.00 [25.00-59.75] years; 125 men [75.3%]). When compared with the 92 patients who received standard care, the 74 patients with TBI who received prehospital plasma had improved 30-day survival even after adjustment for multiple confounders and assessment of the degree of brain injury with clinical variables and biomarkers (hazard ratio [HR], 0.55; 95% CI, 0.33-0.94; P = .03). Receipt of prehospital plasma was associated with improved survival among patients with TBI with a prehospital Glasgow Coma Scale score of less than 8 (HR, 0.56; 95% CI, 0.35-0.91) and those with polytrauma (HR, 0.50; 95% CI, 0.28-0.89). Patients with TBI transported from the scene of injury had improved survival following prehospital plasma administration (HR, 0.45; 95% CI, 0.26-0.80; P = .005), whereas patients who were transferred from an outside hospital showed no difference in survival for the plasma intervention (HR, 1.00; 95% CI, 0.33-3.00; P = .99). Conclusions and Relevance: These findings are exploratory, but they suggest that receipt of prehospital plasma is associated with improved survival in patients with computed tomography-positive TBI. The prehospital setting may be a critical period to intervene in the care of patients with TBI. Future studies are needed to confirm the clinical benefits of early plasma resuscitation following TBI and concomitant polytrauma. Trial Registration: ClinicalTrials.gov Identifier: NCT01818427.

Pre-peritoneal pelvic packing for early hemorrhage control reduces mortality compared to resuscitative endovascular balloon occlusion of the aorta in severe blunt pelvic trauma patients: A nationwide analysis.

BACKGROUND: Early hemorrhage control after severe blunt pelvic trauma is life-saving. The aim of this study is to compare the efficacy and outcomes of pre-peritoneal packing (PPP) and Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) with a subsequent hemorrhage control procedure to control life-threatening pelvic hemorrhage in trauma patients. METHODS: A 3-year (2015-2017) retrospective analysis of the Trauma Quality Improvement Program (TQIP) was performed. All blunt trauma patients (aged ≥15 years) who underwent PPP or Zone 3 REBOA placement were included while deaths on arrival and transfers were excluded. Patients were matched on clinical characteristics using propensity score matching (PSM). Univariate analysis was performed to compare mortality, time to procedure, time in ED, transfusion requirements, complications rates, and ICU and hospital length of stay (LOS) amongst patient groups. RESULTS: Of 420 trauma patients, 307 underwent PPP and 113 REBOA. Patients had similar hemodynamics and ISS upon presentation, but PPP patients had a higher GCS (P = 0.037) and more blunt kidney injuries (P = 0.015). After PSM, 206 trauma patients were included in the analysis. There were no significant differences in blood transfusion, LOS, or major complications. Time to REBOA was shorter than time to PPP (52 vs 77.5 min; P<0.001) with longer time in ED (65 vs 51 min; p = 0.023). The 24-hour (32.4 vs 17.7%; P = 0.23) and in-hospital mortality (52.0 vs 37.3%; P = 0.048) were higher after REBOA. CONCLUSION: PPP is associated with improved survival compared to REBOA placement. Delay in definitive hemorrhage control may provide a potential explanation, but causation remains unresolved. This data suggests that early PPP may offer a benefit over REBOA in the setting of hemorrhage after blunt pelvic trauma. Further, large, multi-institutional studies are warranted to support these findings. LEVEL OF EVIDENCE: Prognostic study, level III.

Reperfusion repercussions: A review of the metabolic derangements following resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Current resuscitative endovascular balloon occlusion of the aorta (REBOA) literature focuses on improving outcomes through careful patient selection, diligent catheter placement, and expeditious definitive hemorrhage control. However, the detection and treatment of post-REBOA ischemia-reperfusion injury (IRI) remains an area for potential improvement. Herein, we provide a review of the metabolic derangements that we have encountered while managing post-REBOA IRI in past swine experiments. We also provide data-driven clinical recommendations to facilitate resuscitation post-REBOA deflation that may be translatable to humans. METHODS: We retrospectively reviewed the laboratory data from 25 swine across three varying hemorrhagic shock models that were subjected to complete REBOA of either 45 minutes, 60 minutes, or 90 minutes. In each model the balloon was deflated gradually following definitive hemorrhage control. Animals were then subjected to whole blood transfusion and critical care with frequent electrolyte monitoring and treatment of derangements as necessary. RESULTS: Plasma lactate peaked and pH nadired long after balloon deflation in all swine in the 45-minute, 60-minute, and 90-minute occlusion models (onset of peak lactate, 32.9 ± 6.35 minutes, 38.8 ± 10.55 minutes, and 49.5 ± 6.5 minutes; pH nadir, 4.3 ± 0.72 minutes, 26.9 ± 12.32 minutes, and 42 ± 7.45 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion models, respectively). All models displayed persistent hypoglycemia for more than an hour following reperfusion (92.1 ± 105.5 minutes, 125 ± 114.9 minutes, and 96 ± 97.8 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion groups, respectively). Hypocalcemia and hyperkalemia occurred in all three groups, with some animals requiring treatment more than an hour after reperfusion. CONCLUSION: Metabolic derangements resulting from REBOA use are common and may worsen long after reperfusion despite resuscitation. Vigilance is required to detect and proactively manage REBOA-associated IRI. Maintaining a readily available "deflation kit" of pharmacological agents needed to treat common post-REBOA electrolyte abnormalities may facilitate management. LEVEL OF EVIDENCE: Level V.

Emerging hemorrhage control and resuscitation strategies in trauma: Endovascular to extracorporeal.

This article reviews four emerging endovascular hemorrhage control and extracorporeal perfusion techniques for management of trauma patients with profound hemorrhagic shock including hemorrhage-induced traumatic cardiac arrest: resuscitative endovascular balloon occlusion of the aorta, selective aortic arch perfusion, extracorporeal life support, and emergency preservation and resuscitation. The preclinical and clinical studies underpinning each of these techniques are summarized. We also present an integrated conceptual framework for how these emerging technologies may be used in the future care of trauma patients in both resource-rich and austere environments.

Intravenous and Intraosseous Blood Transfusion With Three Different Pediatric Pressure Transfusion Strategies in an Immature Swine (Sus scrofa) Model of Hemorrhagic Shock: A Pilot Study.

INTRODUCTION: Exsanguination remains the leading cause of preventable death in military conflicts, and pediatric casualties are common. Transfusion is crucial to preserve life, but vascular access is challenging in children, so intraosseous (IO) access is often required. However, the optimal transfusion method is unclear. There was therefore the need for feasibility testing of a model for contrasting the efficacy of blood infusion devices via intravenous (IV) and IO access in immature swine with bone densities similar to children. MATERIALS AND METHODS: Eighteen immature swine (21 ± 1 kg) were bled 31% of estimated blood volume and then received autologous blood delivered by pressure bag, push-pull (PP), or LifeFlow Rapid Infuser via IO (15-gauge IO needle placed in the humeral head) or IV (auricular 20-gauge), with monitoring for 60 minutes. RESULTS: Flow rates for LifeFlow (172 ± 28 mL/kg) were 4-fold higher than pressure bag (44 ± 13 mL/kg, P < 0.001) and 80% higher than PP (95 ± 28 mL/kg, P < 0.02). However, higher hemolysis was evident in the IV LifeFlow condition, with 6-fold more plasma-free hemoglobin than other conditions (P < 0.0001). CONCLUSIONS: IV LifeFlow conferred higher flows, but higher hemolysis in this pilot study demonstrates the feasibility of an immature swine model toward determining optimal methods for resuscitating children with hemorrhagic shock.

Assessment of the Efficacy and Safety of a Novel, Low-Cost, Junctional Tourniquet in a Porcine Model of Hemorrhagic Shock.

INTRODUCTION: Commercially available junctional tourniquets (JTQs) have several drawbacks. We developed a low-cost, compact, easy to apply JTQ. The aim of this study was to assess the tourniquets' safety and efficacy in a swine model of controlled hemorrhage. MATERIALS AND METHODS: Five pigs were subjected to controlled bleeding of 35% of their blood volume. Subsequently, the JTQ was applied to the inguinal area for 180 minutes. Afterwards, the tourniquet was removed for additional 60 minutes of follow up. During the study, blood flow to both hind limbs and blood samples for tissue damage markers were repeatedly assessed. Following sacrifice, injury to both inguinal areas was evaluated microscopically and macroscopically. RESULTS: Angiography demonstrated complete occlusion of femoral artery flow, which was restored following removal of the tourniquet. No gross signs of tissue damage were noticed. Histological analysis revealed mild necrosis and infiltration of inflammatory cells. Blood tests showed a mild increase in potassium and lactic acid levels throughout the protocol. CONCLUSIONS: The tourniquet achieved effective arterial occlusion with minimal tissue damage, similar to reports of other JTQs. Subjected to further human trials, the tourniquet might be a suitable candidate for widespread frontline deployment because of its versatility, compactness, and affordable design.

The Use of Tranexamic Acid (TXA) for the Management of Hemorrhage in Trauma Patients in the Prehospital Environment: Literature Review and Descriptive Analysis of Principal Themes.

Tranexamic acid (TXA) is an antifibrinolytic agent used to prevent traumatic exsanguination. It was first introduced to clinical practice for the management of patients with bleeding disorders, especially adapted to reduce bleeding in hemophiliacs undergoing oral surgical interventions. TXA exerts its action on the coagulation process by competitively inhibiting plasminogen activation, thereby reducing conversion of plasminogen into plasmin. This ultimately prevents fibrinolysis and reduces hemorrhage. Thus, TXA may be well suited for the management of traumatic hemorrhage in the prehospital setting.Despite multiplicity of studies on the use of TXA in clinical practice, there is no consensus regarding the use of TXA for the management of hemorrhage in trauma patients in the prehospital environment. Thus, a review on this topic was warranted. An extensive literature search yielded 14 full journal articles which met the inclusion criteria. These articles were thoroughly analyzed and the following themes were identified: "dose of TXA administration," "route of TXA administration," "optimal window of TXA administration," "safety of TXA use," "clinical effectiveness of TXA application," and the "feasibility of TXA use in the prehospital setting."Overall, to achieve the best possible outcomes, the literature supports the use of a loading dose of 1 g of TXA, followed by 1 g infusion over 8 h, given by intravenous administration within a 3-h window period of traumatic injury. TXA is very effective and safe to use in the prehospital setting, and its use is clinically and economically feasible.

Training and assessment of competence in resuscitative endovascular balloon occlusion of the aorta (REBOA) - a systematic review.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially life-saving but high-risk emergency procedure in patients with haemorrhagic shock. Lack of physicians with competence in the procedure is a barrier to implementation of REBOA. It is currently unclear how training and assessment of competence should be done. OBJECTIVES: To report and evaluate research in training and assessment of competence in REBOA and femoral arterial access with the aim to investigate the effect of simulation-based training in the procedure and to provide suggestions for the future design of training programs and assessment tools. METHODS: Following PRISMA guidelines, PubMed, Embase, and Cochrane Library databases were searched for studies on training or assessment of competence in REBOA and femoral arterial access. Bias assessment was done using the Medical Education Research Study Quality Instrument. Evidence level was assessed using GRADE. RESULTS: Sixteen studies were included, six of them published as abstracts. Full-text studies included 189 trainees ranging in experience level from military medics to surgical specialists. Outcome measures were heterogenous; the most used were rater checklists, knowledge testing, and procedure time. All studies confirmed an effect of training of REBOA on procedural competence in a simulation setting but had a high degree of bias. No study developed or used an assessment tool supported by validity evidence and no study investigated mid and long-term outcomes. CONCLUSION: Simulation-based training of REBOA improves skills, however, the evidence level is very low and data cannot answer important questions on effect size, skill transfer and retention, and optimal course design. To advance research and training programmes, an assessment tool supported by validity evidence with broad applicability is needed.

Point-of Care Ultrasonographically Guided Proximal External Aortic Compression in the Emergency Department.

In cases of severe subdiaphragmatic vascular trauma, only in extremis interventions such as emergency thoracotomy with aortic cross clamping or resuscitative endovascular balloon occlusion of the aorta are available for temporization until definitive care. This case report proposes a noninvasive approach consisting of localizing the proximal aorta with ultrasonographic guidance and applying a compressive force to occlude the aorta and limit distal flow. Using point-of-care ultrasonography allows precise compression, continuous monitoring of its efficacy, and early detection of return of spontaneous circulation in arrest patients. We present the case of a patient who sustained a gunshot wound causing a left iliac artery injury and subsequent cardiac arrest while he was on route to the hospital. Point-of-care ultrasonographically guided proximal external aortic compression was attempted and return of spontaneous circulation was achieved and maintained, allowing transfer of the patient to the operating room. This single-case report suggests that point-of-care ultrasonographically guided proximal external aortic compression could be used as a bridge to definitive care or to more advanced techniques such as resuscitative endovascular balloon occlusion of the aorta and emergency department thoracotomy with aortic cross clamping.

Platelet-derived- Extracellular Vesicles Promote Hemostasis and Prevent the Development of Hemorrhagic Shock.

Every year more than 500,000 deaths are attributed to trauma worldwide and severe hemorrhage is present in most of them. Transfused platelets have been shown to improve survival in trauma patients, although its mechanism is only partially known. Platelet derived-extracellular vesicles (PEVs) are small vesicles released from platelets upon activation and/or mechanical stimulation and many of the benefits attributed to platelets could be mediated through PEVs. Based on the available literature, we hypothesized that transfusion of human PEVs would promote hemostasis, reduce blood loss and attenuate the progression to hemorrhagic shock following severe trauma. In this study, platelet units from four different donors were centrifuged to separate platelets and PEVs. The pellets were washed to obtain plasma-free platelets to use in the rodent model. The supernatant was subjected to tangential flow filtration for isolation and purification of PEVs. PEVs were assessed by total count and particle size distribution by Nanoparticle Tracking Analysis (NTA) and characterized for cells of origin and expression of EV specific-surface and cytosolic markers by flow cytometry. The coagulation profile from PEVs was assessed by calibrated automated thrombography (CAT) and thromboelastography (TEG). A rat model of uncontrolled hemorrhage was used to compare the therapeutic effects of 8.7 × 108 fresh platelets (FPLT group, n = 8), 7.8 × 109 PEVs (PEV group, n = 8) or Vehicle (Control, n = 16) following severe trauma. The obtained pool of PEVs from 4 donors had a mean size of 101 ± 47 nm and expressed the platelet-specific surface marker CD41 and the EV specific markers CD9, CD61, CD63, CD81 and HSP90. All PEV isolates demonstrated a dose-dependent increase in the rate and amount of thrombin generated and overall clot strength. In vivo experiments demonstrated a 24% reduction in abdominal blood loss following liver trauma in the PEVs group when compared with the control group (9.9 ± 0.4 vs. 7.5 ± 0.5 mL, p < 0.001>). The PEV group also exhibited improved outcomes in blood pressure, lactate level, base excess and plasma protein concentration compared to the Control group. Fresh platelets failed to improve these endpoints when compared to Controls. Altogether, these results indicate that human PEVs provide pro-hemostatic support following uncontrolled bleeding. As an additional therapeutic effect, PEVs improve the outcome following severe trauma by maintaining hemodynamic stability and attenuating the development of ischemia, base deficit, and cardiovascular shock.