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.

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.

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.

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.

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.

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.

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.

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.

Analysis of early treatment of multiple injuries combined with severe pelvic fracture.

PURPOSE: To summarize and analyze the early treatment of multiple injuries combined with severe pelvic fractures, especially focus on the hemostasis methods for severe pelvic fractures, so as to improve the successful rate of rescue for the fatal hemorrhagic shock caused by pelvic fractures. METHODS: A retrospective analysis was conducted in 68 cases of multiple trauma combined with severe pelvic fractures in recent 10 years (from Jan. 2006 to Dec. 2015). There were 57 males and 11 females. Their age ranged from 19 to 75 years, averaging 42 years. Causes of injury included traffic accidents in 34 cases (2 cases of truck rolling), high falling injuries in 17 cases, crashing injuries in 15 cases, steel cable wound in 1 case, and seat belt traction injury in 1 case. There were 31 cases of head injury, 11 cases of chest injury, 56 cases of abdominal and pelvic injuries, and 37 cases of spinal and limb injuries. Therapeutic methods included early anti-shock measures, surgical hemostasis based on internal iliac artery devasculization for pelvic hemorrhage, and early treatment for combined organ damage and complications included embolization and repair of the liver, spleen and kidney, splenectomy, nephrectomy, intestinal resection, colostomy, bladder ostomy, and urethral repair, etc. Patients in this series received blood transfusion volume of 1200-10,000 mL, with an average volume of 2850 mL. Postoperative follow-up ranged from 6 months to 1.5 years. RESULTS: The average score of ISS in this series was 38.6 points. 49 cases were successfully treated and the total survival rate was 72.1%. Totally 19 patients died (average ISS score 42.4), including 6 cases of hemorrhagic shock, 8 cases of brain injury, 1 case of cardiac injury, 2 cases of pulmonary infection, 1 case of pulmonary embolism, and 1 case of multiple organ failure. Postoperative complications included 1 case of urethral stricture (after secondary repair), 1 case of sexual dysfunction (combined with urethral rupture), 1 case of lower limb amputation (femoral artery thrombosis), and 18 cases of consumptive coagulopathy. CONCLUSION: The early treatment of multiple injuries combined with severe pelvic fractures should focus on pelvic hemostasis. Massive bleeding-induced hemorrhagic shock is one of the main causes of poor prognosis. The technique of internal iliac artery devasculization including ligation and embolization can be used as an effective measure to stop or reduce bleeding. Consumptive coagulopathy is difficult to deal with, which should be detected and treated as soon as possible after surgical measures have been performed. The effect of using recombinant factor VII in treating consumptive coagulopathy is satisfactory.

Effects of the establishment of a trauma center and a new protocol on patients with hemodynamically unstable pelvic fractures at a single institution in Korea.

PURPOSE: The aim of this study was to determine whether the outcomes of patients with hemodynamically unstable pelvic bone fractures changed after the introduction of a protocol including extraperitoneal pelvic packing (EPP) and the establishment of a trauma center. METHODS: We analyzed data of adult patients (≥ 18 years old) with hemodynamically unstable pelvic bone fractures who visited a single trauma center from February 2009 to October 2016. In July 2014, a new protocol for pelvic fractures was implemented, and a trauma center was established. Therefore, patient outcomes were compared by period (period I: pre-protocol vs. period II: post-protocol). RESULTS: Seventy-nine patients with hemodynamically unstable pelvic bone fractures were recruited. The time to angiographic embolization after arrival at the emergency room decreased significantly in period II when compared to period I (182.9 vs. 268.9 min, respectively, p < 0.001). The time required to intervention, including EPP, also decreased, from 268.9 ± 132.4 min in period I to 141.9 ± 79.9 min in period II (p < 0.001). The overall mortality rate decreased from 47.2% in period I to 23.3% in period II (p = 0.033), and mortality related to hemorrhagic shock in particular, was significantly lowered, from 27.8% in period I to 4.7% in period II (p = 0.009). CONCLUSIONS: The establishment of a trauma center and the implementation of a new protocol that included EPP were effective in the treatment of patients with hemodynamically unstable pelvic fractures.

No. 115-Hemorrhagic Shock.

OBJECTIVE: To review the clinical aspects of hemorrhagic shock and provide recommendations for therapy. OPTIONS: Early recognition of hemorrhagic shock and prompt systematic intervention will help avoid poor outcomes. OUTCOMES: Establish guidelines to assist in early recognition of hemorrhagic shock and to conduct resuscitation in an organized and evidence-based manner. EVIDENCE: Medline references were sought using the MeSH term "hemorrhagic shock." All articles published in the disciplines of obstetrics and gynaecology, surgery, trauma, critical care, anesthesia, pharmacology, and hemotology between 1 January 1990 and 31 August 2000 were reviewed, as well as core textbooks from these fields. Selected references from these articles and book chapters were also obtained and reviewed. The level of evidence has been determined using the criteria described by the Canadian Task Force on Preventive Health Care. VALIDATION: These guidelines have been reviewed by the Clinical Practice Obstetrics Committee and approved by Executive and Council of the Society of Obstetricians and Gynaecologists of Canada. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada.

Nicotinamide mononucleotide preserves mitochondrial function and increases survival in hemorrhagic shock.

Hemorrhagic shock depletes nicotinamide adenine dinucleotide (NAD) and causes metabolic derangements that, in severe cases, cannot be overcome, even after restoration of blood volume and pressure. However, current strategies to treat acute blood loss do not target cellular metabolism. We hypothesized that supplemental nicotinamide mononucleotide (NMN), the immediate biosynthetic precursor to NAD, would support cellular energetics and enhance physiologic resilience to hemorrhagic shock. In a rodent model of decompensated hemorrhagic shock, rats receiving NMN displayed significantly reduced lactic acidosis and serum IL-6 levels, two strong predictors of mortality in human patients. In both livers and kidneys, NMN increased NAD levels and prevented mitochondrial dysfunction. Moreover, NMN preserved mitochondrial function in isolated hepatocytes cocultured with proinflammatory cytokines, indicating a cell-autonomous protective effect that is independent from the reduction in circulating IL-6. In kidneys, but not in livers, NMN was sufficient to prevent ATP loss following shock and resuscitation. Overall, NMN increased the time animals could sustain severe shock before requiring resuscitation by nearly 25% and significantly improved survival after resuscitation (P = 0.018), whether NMN was given as a pretreatment or only as an adjunct during resuscitation. Thus, we demonstrate that NMN substantially mitigates inflammation, improves cellular metabolism, and promotes survival following hemorrhagic shock.

A systematic review and meta-analysis of the use of resuscitative endovascular balloon occlusion of the aorta in the management of major exsanguination.

BACKGROUND: Circulatory collapse is a leading cause of mortality among traumatic major exsanguination and in ruptured aortic aneurysm patients. Approximately 40% of patients die before hemorrhage control is achieved. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive surgical or endovascular repair. A systematic review was conducted for the current clinical use of REBOA in patients with hemodynamic instability and to discuss its potential role in improving prehospital and in-hospital outcome. METHODS: Systematic review and meta-analysis (1900-2017) using MEDLINE, Cochrane, EMBASE, Web of Science and Central and Emcare using the keywords "aortic balloon occlusion", "aortic balloon tamponade", "REBOA", and "Resuscitative Endovascular Balloon Occlusion" in combination with hemorrhage control, hemorrhage, resuscitation, shock, ruptured abdominal or thoracic aorta, endovascular repair, and open repair. Original published studies on human subjects were considered. RESULTS: A total of 490 studies were identified; 89 met criteria for inclusion. Of the 1436 patients, overall reported mortality was 49.2% (613/1246) with significant differences (p < 0.001) between clinical indications. Hemodynamic shock was evident in 79.3%, values between clinical indications showed significant difference (p < 0.001). REBOA was favored as treatment in trauma patients in terms of mortality. Pooled analysis demonstrated an increase in mean systolic pressure by almost 50 mmHg following REBOA use. CONCLUSION: REBOA has been used in trauma patients and ruptured aortic aneurysm patients with improvement of hemodynamic parameters and outcomes for several decades. Formal, prospective study is warranted to clarify the role of this adjunct in all hemodynamic unstable patients.

Could resuscitative endovascular balloon occlusion of the aorta improve survival among severely injured patients with post-intubation hypotension?

Current literature shows the association of post-intubation hypotension and increased odds of mortality in critically ill non-trauma and trauma populations. However, there is a lack of research on potential interventions that can prevent or ameliorate the consequences of endotracheal intubation and thus improve the prognosis of trauma patients with post-intubation hypotension. This review paper hypothesizes that the deployment of REBOA among trauma patients with PIH, by its physiologic effects, will reduce the odds of mortality in this population. The objective of this paper is to review the current literature on REBOA and post-intubation hypotension, and, furthermore, to provide a rational hypothesis on the potential role of REBOA in severely injured patients with post-intubation hypotension.

Prophylactic use of resuscitative endovascular balloon occlusion of the aorta in women with abnormal placentation: A systematic review, meta-analysis, and case series.

BACKGROUND: We describe intraoperative and postdischarge outcomes of a case series after the prophylactic use of resuscitative endovascular balloon occlusion of the aorta (REBOA) during elective cesarean delivery in pregnant women with morbidly adherent placenta (MAP). We furthermore performed a systematic review and meta-analysis to investigate the safety and effectiveness of the use of REBOA during elective cesarean delivery in pregnant women with MAP. METHODS: Descriptive case series of REBOA (December 2015 to June 2017) used during elective cesarean delivery in pregnant women with MAP. The systematic review was conducted following PRISMA guidelines. We included studies involving pregnant women with a diagnosis of MAP who underwent an elective cesarean delivery with prophylactic REBOA placement. A meta-analysis was performed to assess the overall amount of transfusions and intraoperative hemorrhage of REBOA compared to NO-REBOA cases. RESULTS: A total of 12 patients with MAP underwent elective cesarean delivery with REBOA deployment. The median (interquartile range) of packed red blood cells transfused during the first 24 hours following surgery was two units (0-3.5). The median (interquartile range) of intraoperative blood loss was 1,500 mL (900-2,750). At 28 days, all patients were alive, and no adverse outcomes were observed. Four articles were included in the systematic review and meta-analysis. These articles included a total of 441 patients. Quantitative synthesis (meta-analysis) found that the use of REBOA as prophylaxis for the prevention of major hemorrhage was associated with a lower amount of intraoperative hemorrhage (in milliliters) (weighted mean difference, -1,384.66; 95% confidence interval, -2,141.74 to -627.58) and lower requirements of blood products transfusions (in units) (weighted mean difference, -2.42; 95% confidence interval, -3.90 to -0.94). CONCLUSION: We provide clinical data supporting the use of REBOA in the management of pregnant women with MAP undergoing elective cesarean delivery. Our findings demonstrate the feasibility of REBOA as a prophylactic intervention to improve outcomes in women at risk of catastrophic postpartum hemorrhage. LEVEL OF EVIDENCE: Therapeutic study, level V; Systematic Review, level IV.

Use of interventional radiology as initial hemorrhage control to improve outcomes for potentially lethal multiple blunt injuries.

INTRODUCTION: Recently, trauma management has been markedly improved with interventional radiology (IVR) and damage-control strategies. However, the indications for its use in hemodynamically unstable patients with severe trauma remains unclear. In some cases, IVR may be more effective than surgery for damage-control hemostasis; however, performing IVR in life-threatening trauma settings is challenging. To address this, we practiced and evaluated a trauma-management system with emergency physicians who trained for both severe trauma management, and techniques of surgery and IVR. MATERIALS AND METHODS: Among the 1822 patients with severe trauma admitted between October 2014 and December 2016, 201 underwent emergency surgery or IVR. Among these, 16 patients whose systolic blood pressure was ≤90 mmHg, without improvement following primary resuscitation, and whose first intervention was IVR, were analyzed. We retrospectively evaluated the admission characteristics, IVR-related characteristics, and prognoses, and compared several parameters before and after IVR. RESULTS: This study included 10 men and 6 women (median age: 46 years). IVR was performed for 10 pelvic fractures; five liver-, one splenic-, and one renal injury; and one transection each of the external carotid-, vertebral-, axillosubclavian-, intercostal-, and lumbar arteries. The mean times from the patient arrival, and diagnosis to the start of IVR were 56.3 ±â€¯26.6 and 15.1 ±â€¯3.8 min, respectively. The mean time spent in the angiography suite was 50 min. The systolic blood pressure, pulse rate, base excess/deficit, serum-lactate levels, and D-dimer values were significantly improved after IVR. Although two patients needed additional treatment for morbidities following IVR intervention, all achieved complete recovery. The mortality rate was 25.0%, and no preventable deaths were noted. Eight patients showed unexpected survival. CONCLUSIONS: In some cases, IVR may be the best first measure for resuscitative hemostasis in potentially lethal multiple injuries, given efficient diagnoses/actions and the ability to deal with complications.

Tubastatin A prevents hemorrhage-induced endothelial barrier dysfunction.

BACKGROUND: Microvascular hyperpermeability resulting from endothelial barrier dysfunction (EBD) is associated with worse clinical outcomes in trauma-induced hemorrhagic shock. We have previously shown that treatment with Tubastatin A (TubA), a histone deacetylase 6 inhibitor, improves outcomes in animal models of shock. In this study, we investigate whether TubA treatment may prevent trauma-related EBD. METHODS: Wistar-Kyoto rats subjected to 40% hemorrhage were treated with TubA or vehicle control. Acute lung injury (ALI) was assessed histologically from tissues harvested 6 hours posthemorrhage. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured in EGM BulletKit medium. Medium was exchanged for glucose-free Dulbecco's Modified Eagle Medium (0.5% fetal bovine serum) with or without TubA, and cells were placed in an anoxic chamber (5% CO2, 95% N2, 20-48 hours). Expression of acetylated tubulin and hypoxia-inducible factor 1α was measured by Western blot. Soluble Intercellular Adhesion Molecule-1 concentration within the medium, a marker of endothelial integrity, was determined using enzyme-linked immunosorbent assay. Monolayers were assessed for permeability via transwell assays using fluorescein isothiocyanate-labeled albumin. RESULTS: Rats treated with TubA had significantly reduced ALI relative to vehicle control. In vitro, TubA significantly attenuated anoxia-induced hyperpermeability, hypoxia-inducible factor 1α expression, and glycocalyx shedding. CONCLUSIONS: Our findings demonstrate that TubA prevents hemorrhage-induced ALI in rats. Additionally, we have shown that TubA prevents anoxia-induced EBD in vitro. Taken together, these results suggest that TubA could attenuate microvascular hyperpermeability related to hemorrhagic shock.