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Background: Assessment of the volemic loss is a major challenge during the management of hemorrhagic shock. Echocardiography is an increasingly used noninvasive tool for hemodynamic assessment. In mechanically ventilated patients, some studies suggest that respiratory variations of mean subaortic time-velocity integral (∆VTI) would be predictive of fluid filling response. An experimental model of controlled hemorrhagic shock provides a precise approach to study correlation between blood volume and cardiac ultrasonographic parameters., Objectives: The main objective was to analyze the ∆VTI changes during hemorrhage in an anesthetized-piglet model of controlled hemorrhagic shock. The secondary objective was to evaluate ∆VTI during the resuscitation process after hemorrhage and other echocardiographic parameters changes during the whole protocol., Methods: Twenty-four anesthetized and ventilated piglets were bled until mean arterial pressure reached 40 mm Hg. Controlled hemorrhage was maintained for 30 minutes before randomizing the piglets to two resuscitation groups: fluid filling group resuscitated with saline solution and noradrenaline group resuscitated with saline solution and noradrenaline. Echocardiography and hemodynamic measures, including pulsed pressure variations (PPV), were performed at different stages of the protocol., Results: The correlation coefficient between ΔVTI and PPV with the volume of bleeding during the hemorrhagic phase were respectively 0.24 (95% confidence interval, 0.08-0.39; p < 0.01) and 0.57 (95% CI, 0.44-0.67; p < 0.01). Two parameters had a moderate correlation coefficient with hemorrhage volume (over 0.5): mean subaortic time-velocity index (VTI) and mitral annulus diastolic tissular velocity (E')., Conclusion: In this hemorrhagic shock model, ΔVTI had a low correlation with the volume of bleeding, but VTI and E' had a correlation with blood volume comparable to that of PPV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare early outcomes and 24-hour survival after LVR with the novel polyethylene glycol-20k-based crystalloid (PEG-20k), WB, or hextend in a preclinical model of lethal HS., Background: Posttraumatic HS is a major cause of preventable death. current resuscitation strategies focus on restoring oxygen-carrying capacity (OCC) and coagulation with blood products. Our lab shows that PEG-20k is an effective non-sanguineous, LVR solution in acute models of HS through mechanisms targeting cell swelling-induced microcirculatory failure., Methods: Male pigs underwent splenectomy followed by controlled hemorrhage until lactate reached 7.5-8.5 mmol/L. They were randomized to receive LVR with PEG-20k, WB, or Hextend. Surviving animals were recovered 4 hours post-LVR. Outcomes included 24-hour survival rates, mean arterial pressure, lactate, hemoglobin, and estimated intravascular volume changes., Results: Twenty-four-hour survival rates were 100%, 16.7%, and 0% in the PEG-20k, WB, and Hextend groups, respectively (P= 0.001). PEG-20k significantly restored mean arterial press, intravascular volume, and capillary perfusion to baseline, compared to other groups. This caused complete lactate clearance despite decreased OCC. Neurological function was normal after next-day recovery in PEG-20k resuscitated pigs., Conclusion: Superior early and 24-hour outcomes were observed with PEG-20k LVR compared to WB and Hextend in a preclinical porcine model of lethal HS, despite decreased OCC from substantial volume-expansion. These findings demonstrate the importance of enhancing microcirculatory perfusion in early resuscitation strategies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Targeted regional optimization (TRO) describes partial resuscitative endovascular balloon occlusion of the aorta strategy that allows for controlled distal perfusion to balance hemostasis and tissue perfusion. This study characterized hemodynamics at specific targeted distal flow rates in a swine model of uncontrolled hemorrhage to determine if precise TRO by volume was possible., Methods: Anesthetized swine were subjected to liver laceration and randomized into TRO at distal flows of 300 mL/min (n = 8), 500 mL/min (n = 8), or 700 mL/min (n = 8). After 90 min, the animals received damage control packing and were monitored for 6 h. Hemodynamic parameters were measured continuously, and hematology and serologic labs obtained at predetermined intervals., Results: During TRO, the average percent deviation from the targeted flow was lower than 15.9% for all cohorts. Average renal flow rates were significantly different across all cohorts during TRO phase (P < 0.0001; TRO300 = 63.1 ± 1.2; TRO500 = 133.70 ± 1.93; TRO700 = 109.3 ± 2.0), with the TRO700 cohort having less renal flow than TRO500. The TRO500 and TRO700 average renal flow rates inverted during the intensive care unit phase (P < 0.0001; TRO300 = 86.20 ± 0.40; TRO500 = 148.50 ± 1.45; TRO700 = 181.1 ± 0.70). There was higher blood urea nitrogen, creatinine, and potassium in the TRO300 cohort at the end of the experiment, but no difference in lactate or pH between cohorts., Conclusion: This study demonstrated technical feasibility of TRO as a strategy to improve outcomes after prolonged periods of aortic occlusion and resuscitation in the setting of ongoing solid organ hemorrhage. A dose-dependent ischemic end-organ injury occurs beginning with partial aortic occlusion that progresses through the critical care phase, with exaggerated effect on renal function., (Copyright © 2022 by the Shock Society.)

A 68-year-old man was transferred to our hospital because of sudden right costal pain with unmeasurable hypotension. Ultrasonography revealed possible hemorrhagic shock due to ruptured hepatocellular carcinoma (HCC). As the patient was not hemodynamically stable after primary treatment, resuscitative endovascular balloon occlusion of the aorta (REBOA) was performed, and hemodynamic stability was then achieved. Contrast-enhanced computed tomography confirmed the diagnosis. Transcatheter artery embolization with gelatin sponge particles and coils eliminated the extravasation. The patient was discharged on day 36 post-procedure. Our observations suggest that REBOA may help achieve hemodynamic stability in cases of ruptured HCC.

Uncontrolled hemorrhage is a leading cause of death in trauma situations. Developing solutions to automate hemorrhagic shock resuscitation may improve the outcomes for trauma patients. However, testing and development of automated solutions to address critical care interventions, oftentimes require extensive large animal studies for even initial troubleshooting. The use of accurate laboratory or in-silico models may provide a way to reduce the need for large animal datasets. Here, a tabletop model, for use in the development of fluid resuscitation with physiologically relevant pressure-volume responsiveness for high throughput testing, is presented. The design approach shown can be applied to any pressure-volume dataset through a process of curve-fitting, 3D modeling, and fabrication of a fluid reservoir shaped to the precise curve fit. Two case studies are presented here based on different resuscitation fluids: whole blood and crystalloid resuscitation. Both scenarios were derived from data acquired during porcine hemorrhage studies, used a pressure-volume curve to design and fabricate a 3D model, and evaluated to show that the test platform mimics the physiological data. The vessels produced based on data collected from pigs infused with whole blood and crystalloid were able to reproduce normalized pressure-volume curves within one standard deviation of the porcine data with mean residual differences of 0.018 and 0.016, respectively. This design process is useful for developing closed-loop algorithms for resuscitation and can simplify initial testing of technologies for this life-saving medical intervention., (© 2022 IOP Publishing Ltd.)

Purpose of Review: Trauma resuscitation management has evolved over the years with a more nuanced understanding of the injured patient's physiologic state of shock. The purpose of this review is to discuss the role of whole blood administration in the prehospital setting in the resuscitation of the trauma patient., Recent Findings: In traumatically injured patients, whole blood administration initiated in the prehospital setting may improve early shock severity, coagulopathy, and survival when used over traditional resuscitation fluids such as crystalloid administration or component therapy., Summary: The timing of resuscitation and its components deserve special attention when improving outcomes for trauma patients requiring massive transfusion., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Targeted regional optimization (TRO), a partial resuscitative endovascular balloon occlusion of the aorta strategy, may mitigate distal ischemia and extend the window of effectiveness for this adjunct. An automated device may allow greater control and precise regulation of flow past the balloon, while being less resource-intensive. The objective of this study was to assess the technical feasibility of the novel advanced partial occlusion controller (APOC) in achieving TRO at multiple distal pressures., Methods: Female swine (n = 48, 68.1 ± 0.7 kg) were randomized to a target distal mean arterial pressure (MAP) of 25 mm Hg, 35 mm Hg, or 45 mm Hg by either manual (MAN) or APOC regulation (n = 8 per group). Uncontrolled hemorrhage was generated by liver laceration. Targeted regional optimization was performed for 85 minutes, followed by surgical control and a 6-hour critical care phase. Proximal and distal MAP and flow rates were measured continuously., Results: At a target distal MAP of 25 mm Hg, there was no difference in the MAP attained (APOC: 26.2 ± 1.05 vs. MAN: 26.1 ± 1.78 mm Hg) but the APOC had significantly less deviance (10.9%) than manual titration (14.9%, p < 0.0001). Similarly, at a target distal MAP of 45 mm Hg, there was no difference in mean pressure (44.0 ± 0.900 mm Hg vs. 45.2 ± 1.31 mm Hg) but APOC had less deviance (9.34% vs. 11.9%, p < 0.0001). There was no difference between APOC and MAN in mean (34.6 mm Hg vs. 33.7 mm Hg) or deviance (9.95% vs. 10.4%) at a target distal MAP of 35 mm Hg, respectively. The APOC made on average 77 balloon volume adjustments per experiment compared with 29 by manual titrations., Conclusion: The novel APOC consistently achieved and sustained precisely regulated TRO across all groups and demonstrated reduced deviance at the 25 mm Hg and 45 mm Hg groups compared with manual titration., (Copyright © 2021 American Association for the Surgery of Trauma.)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potential adjunct in pediatric trauma patients with noncompressible truncal and pelvic hemorrhage; however, there are little data evaluating the anatomic considerations of REBOA in children. We evaluated the vascular dimensions and anatomic limitations of using REBOA in children., Methods: Computed tomography scans of pediatric patients performed between February 2016 and October 2019 were retrospectively reviewed by two investigators. Vascular measurements included diameters of aorta zones I and III, common iliac arteries, external iliac arteries, and common femoral arteries (CFAs), and distances between access site (CFA) and aorta zones I and III. Measurements were grouped within Broselow categories, based upon patient height. Interrater reliability for measurements was determined using intraclass correlation coefficients. Vascular dimensions were correlated with the patient's height, weight, and body mass index using linear regression analysis., Results: A total of 557 computed tomography scans met the inclusion criteria and were reviewed. Measurements of vessel diameter and distance from the CFA to aorta zones I and III were determined and grouped by Broselow category. Patient age ranged from 0 to 18 years, with a male to female ratio of 1:1. Overall interrater reliability of vessel measurements was good (average intraclass correlation coefficient, 0.90). Vessel diameter had greatest correlation with height (R2 = 0.665, aorta zone I; R2 = 0.611, aorta zone III) and poorly correlated with body mass index (R2 = 0.318 and R2 = 0.290, respectively)., Conclusion: This study represents the largest compilation of REBOA-related pediatric vessel diameter measurements and the first to provide data on distance between access site and balloon deployment zones. Based on our findings, the 7-Fr REBOA catheter would be appropriate for the Black, Green, and Orange Broselow categories, and a 4-Fr REBOA catheter would be warranted for Yellow, White, and Blue Broselow categories., Level of Evidence: Prognostic and epidemiological, level III., (Copyright © 2022 American Association for the Surgery of Trauma.)

Background: Minimally invasive resuscitative endovascular balloon occlusion of the aorta (REBOA) following noncompressible hemorrhage results in significant ischemia reperfusion injury (IRI). Adverse outcomes from IRI include organ dysfunction and can result in profound hemodynamic and molecular compromise. We hypothesized that adenosine, lidocaine, and magnesium (ALM) attenuates organ injury and inflammation responses following REBOA IRI in a porcine model of hemorrhage., Methods: Animals underwent a 20% controlled hemorrhage followed by 45 minutes of supraceliac balloon occlusion. They were randomized into two groups: control (n = 9) and ALM intervention (n = 9) to include a posthemorrhage, pre-REBOA bolus (200 mL of 3% NaCl ALM) followed by a continuous drip (2 mL/kg per hour of 0.9% NaCl ALM) during the 4-hour resuscitative period. Primary outcomes included hemodynamic parameters, gene expression of inflammatory signaling molecules, and plasma concentrations of select cytokines and chemokines., Results: The ALM cohort demonstrated a significant reduction in cardiac output and cardiac index. Plasma concentrations of interleukin 2 and interleukin 10 were significantly lower 3 hours post-REBOA in animals treated with ALM versus vehicle. Interleukin 4 levels in plasma were also lower with ALM at 3 and 4 hours post-REBOA (p < 0.05). Liver expression of IL1RN, MTOR, and LAMP3 messenger RNA was significantly lower with ALM as compared with the vehicle. No significant difference in large bowel gene expression was observed between treatments., Conclusion: In a porcine model of hemorrhage, ALM treatment mitigated inflammatory responses early during post-REBOA resuscitation. Our findings suggest that ALM use with trauma may reduce inflammatory injury and improve outcomes related to REBOA utilization., (Copyright © 2021 American Association for the Surgery of Trauma.)

Trauma is the leading cause of non-obstetrical maternal death. A 19-year-old woman at 20 weeks' gestation was brought to the emergency room after suffering a gunshot wound to the lower abdomen. Upon arrival, she was hemodynamically stable and imaging was obtained. CT revealed a rupture of the uterus with a partially extrauterine fetus, and the patient was immediately taken for an explorative laparotomy. Prior to the surgical start, the patient's blood pressure declined and, subsequently, a resuscitative endovascular balloon occlusion of the aorta (REBOA) was placed. The fetus and placenta were delivered and both uterine arteries and the inferior epigastric artery were ligated. Following an unremarkable postoperative course, she was discharged on hospital day 17. The mainstay approach to trauma in pregnancy should be to utilize focused imaging techniques to assess extent of trauma and provide adequate circulation to vital organs. Aortic balloon occlusion may be considered as a viable strategy to enhance resuscitation.

Background: Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock., Methods: Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938., Findings: From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths., Interpretation: The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders., Funding: National Institute for Health Research Efficacy and Mechanism Evaluation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Direct peritoneal resuscitation (DPR) has been used to help preserve microcirculation by reversing vasoconstriction and hypoperfusion associated with the pathophysiological process of shock, which can occur despite appropriate intravenous resuscitation. This approach depends on infusing a hyperosmolar solution intraperitoneally via a percutaneous catheter with the tip ending near the pelvis or the root of the mesentery. The abdomen is usually left open with a negative pressure abdominal dressing to continuously evacuate the infused dialysate. Hypertonicity of the solution triggers visceral vasodilation to help maintain blood flow, even during shock, and is also associated with reduced local inflammatory cytokines and other mediators, preservation of endothelial cell function, and mitigation of organ edema and necrosis. It also has a direct effect on liver perfusion and edema, more rapidly corrects electrolyte abnormalities compared to intravenous resuscitation alone, and may requireless intravenous fluid to stabilize blood pressure, all of which shortens the time required to close patients' abdomen., Methods: An online query using the search term "direct peritoneal resuscitation" was carried out in PubMed, MEDLINE and SciELO, limited to publications indexed from January 2014 to June 2020. Of the 20 articles returned, full text was able to be obtained for 19. A manual review of included articles' references was resulted in the addition of 1 article, for a total of 20 included articles., Results: The 20 articles were comprised of 15 animal studies, 4 clinical studies,and 1 expert opinion. The benefits include both local and possibly systemic effects on perfusion, hypoxia, acidosis, and inflammation, and are associated with improved outcomes and reduced complications., Conclusion: DPR shows promise in patients with hemorrhagic shock, septic shock, and other conditions resulting in an open abdomen after damage control laparotomy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Use of whole blood (WB) for trauma resuscitation has seen a resurgence. The purpose of this study was to investigate survival benefit of WB across a diverse population of bleeding trauma patients., Study Design: A prospective observational cohort study of injured patients receiving emergency-release blood products was performed. All adult trauma patients resuscitated between November 2017 and September 2020 were included. The WB group included patients receiving any group O WB units. The component (COMP) group received no WB units, instead relying on fractionated blood (red blood cells, plasma, and platelets). Univariate and multivariate analyses were performed. Given large observed differences in our regression model, post hoc adjustments with inverse probability of treatment were conducted and a propensity score created. Propensity scoring and Poisson regression supported these findings., Results: Of 1,377 patients receiving emergency release blood products, 840 received WB and 537 remained in the COMP arm. WB patients had higher Injury Severity Score (ISS; 27 vs 20), lower field blood pressure (103 vs 114), and higher arrival lactate (4.2 vs 3.5; all p < 0.05). Postarrival transfusions and complications were similar between groups, except for sepsis, which was lower in the WB arm (25 vs 30%, p = 0.041). Although univariate analysis noted similar survival between WB and COMP (75 vs 76%), logistic regression found WB was independently associated with a 4-fold increased survival (odds ratio [OR] 4.10, p < 0.001). WB patients also had a 60% reduction in overall transfusions (OR 0.38, 95% CI 0.21-0.70). This impact on survival remained regardless of location of transfusion, ISS, or presence of head injury., Conclusion: In patients experiencing hemorrhagic shock, WB transfusion is associated with both improved survival and decreased overall blood utilization., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is controversial as a hemorrhage control adjunct due to lack of data with a suitable control group. We aimed to determine outcomes of trauma patients in shock undergoing REBOA versus no-REBOA., Methods: This single-center, retrospective, matched cohort study analyzed patients ≥16 years in hemorrhagic shock without cardiac arrest (2000-2019). REBOA (R; 2015-2019) patients were propensity matched 2:1 to historic (H; 2000-2012) and contemporary (C; 2013-2019) groups. In-hospital mortality and 30-day survival were analyzed using chi-squared and log rank testing, respectively., Results: A total of 102,481 patients were included (R = 57, C = 88,545, H = 13,879). Propensity scores were assigned using age, race, mechanism, lowest systolic blood pressure, lowest Glasgow Coma Score (GCS), and body region Abbreviated Injury Scale scores to generate matched groups (R = 57, C = 114, H = 114). In-hospital mortality was significantly lower in the REBOA group (19.3%) compared to the contemporary (35.1%; p = 0.024) and historic (44.7%; p = 0.001) groups. 30-day survival was significantly higher in the REBOA versus no-REBOA groups., Conclusion: In a high-volume center where its use is part of a coordinated hemorrhage control strategy, REBOA is associated with improved survival in patients with noncompressible torso hemorrhage., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Jonathan J Morrison is on the Medical Advisory Board of Prytime Medical. The remainder of the authors have no conflicts of interest to report.

Background: Gastrointestinal involvement is not uncommon in patients with disseminated talaromycosis, but successful management of massive gastrointestinal bleeding and hemorrhagic shock secondary to talaromycosis is rarely reported. Clinical management strategies for these patients have not been well documented., Case Presentation: Here, we reported a case of disseminated talaromycosis with recurrent gastrointestinal bleeding and hemorrhagic shock who was successfully alleviated solely with medical treatment., Conclusions: Early diagnosis and treatment for Talaromyces marneffei, intravenous fluid resuscitation, hemostatic therapy and blood transfusion are all essential for talaromycosis complicated with gastrointestinal bleeding and hemorrhagic shock. It is also necessary to warn about the possibility of bleeding induced or aggravated by endoscopic biopsy trauma., (© 2022. The Author(s).)

Purpose: Our goal was to describe resuscitation practices in critically ill medical patients with active hemorrhage requiring large volume resuscitation and identify factors associated with poor outcomes., Patients and Methods: This was a single center retrospective observational cohort study. Patients admitted to the medical intensive care unit from 2011 to 2017 who received ≥5 units of packed red blood cells (pRBCs) within 24 h were included. Data including volume of blood products and crystalloid administered, baseline sequential organ failure assessment (SOFA) scores, and outcomes were abstracted. Univariate and multivariate analyses were performed to determine clinical factors associated with hospital mortality., Results: Two hundred forty-six patients were identified. Mean volumes of 2,448 mL of pRBCs and 3.9L of crystalloid were transfused over 24 h. Inpatient mortality for the entire cohort was 48%. Multivariable analysis identified factors associated with hospital mortality; higher BMI (OR 1.047, 95% CI 1.013-1.083), higher ratio of fresh frozen plasma (FFP) to pRBCs (OR 2.744, 95% CI 1.1-6.844), and higher baseline SOFA scores (OR 1.3, 95% CI 1.175-1.437)., Conclusion: In a cohort of critically ill medical patients undergoing resuscitation for hemorrhage, higher BMI, increased ratio of FFP to pRBCs, and higher SOFA scores were associated with increased mortality. Further studies are needed to clarify resuscitation practices associated with outcomes in this population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Objective: Fluid resuscitation is a crucial step in shock treatment, but the choice of crystal solution remains controversial. Sodium bicarbonated Ringer's solution can not only effectively expand blood volume, but also reduce tissue damage and acidosis. The study aims to evaluate the resuscitation effect of sodium bicarbonated Ringer's solution on patients with hemorrhagic shock., Patients and Methods: A total of 96 patients with hemorrhagic shock were randomly assigned to receive either normal saline solution (control group) or sodium bicarbonated Ringer's solution (experimental group). The changes in blood lactate, heart rate, arterial pH and mean arterial pressure (MAP) were measured at different time points. The 28-day survival rate, the incidence of complications, and the average length of hospital stay were recorded. Simult RESULTS: The heart rate, blood lactate, sodium, and chloride in the experimental group were significantly lower than those in the control group, while the MAP, potential of hydrogen (pH), bicarbonate, and base excess in the experimental group were significantly higher than those in the control group at every observed time point after resuscitation (p<0.05). Compared with the control group, the experimental group had a lower incidence of acute respiratory distress syndrome (ARDS) (8.3% vs. 22.9%, p<0.05), shorter mechanical ventilation time (2.2 vs. 3.5, p<0.05), and shorter intensive care unit length of stay (3.8 vs. 4.1, p<0.05). The 28-day survival rate between the two groups showed no significant differences (p>0.05)., Conclusions: Early resuscitation with sodium bicarbonated Ringer's solution could better maintain acid-base balance and hemodynamic stability and reduce the risk of related complications.

Background: Massive transfusion with older packed red blood cells is associated with increased morbidity and mortality. As packed red blood cells age, they undergo biochemical and structural changes known as the storage lesion. We developed a novel solution to increase viscosity in stored packed red blood cells. We hypothesized that packed red blood cell storage in this solution would blunt storage lesion formation and mitigate the inflammatory response after resuscitation., Methods: Blood was obtained from 8- to 10-week-old C57BL/6 male donor mice or human volunteers and stored as packed red blood cell units for 14 days for mice or 42 days for humans in either standard AS-3 storage solution or EAS-1587, the novel packed red blood cell storage solution. Packed red blood cells were analyzed for microvesicles, cell-free hemoglobin, phosphatidylserine, band-3 protein, glucose utilization, and osmotic fragility. Additional mice underwent hemorrhage and resuscitation with packed red blood cells stored in either AS-3 or EAS-1587. Serum was analyzed for inflammatory markers., Results: Murine packed red blood cells stored in EAS-1587 demonstrated reductions in microvesicle and cell-free hemoglobin accumulation as well as preserved band-3 expression, increase glucose utilization, reductions in phosphatidylserine expression, and susceptibility to osmotic stress. Serum from mice resuscitated with packed red blood cells stored in EAS-1587 demonstrated reduced proinflammatory cytokines. Human packed red blood cells demonstrated a reduction in microvesicle and cell-free hemoglobin as well as an increase in glucose utilization., Conclusion: Storage of packed red blood cells in a novel storage solution mitigated many aspects of the red blood cell storage lesion as well as the inflammatory response to resuscitation after hemorrhage. This modified storage solution may lead to improvement of packed red blood cell storage and reduce harm after massive transfusion., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Splenic hemorrhagic shock is a typical emergency in surgery, seriously threatening human beings' life. Emerging evidence shows that microRNAs (miRNAs) are closely related to inflammation and immunity in the body. However, the detailed effects and underlying mechanisms of miRNAs on the immune function of splenic hemorrhagic shock have not been revealed yet. In the present study, we construct the rat hemorrhagic shock model, and the rats are further cured with splenic blood transport clipping recanalization (SBTCR). MiR-18b-5p was highly expressed in the spleen of hemorrhagic shock rats detected by the qRT-PCR assay. Functionally, down-regulation of miR-18b-5p notably inhibited the levels of SOD1, iNOS and IL-6 in macrophages isolated from splenic tissues detected by qRT-PCR and ELISA assays. In addition, inhibition of miR-18b-5p significantly decreased the M1/M2 ratio of macrophages. Besides, knockdown of miR-18b-5p obviously reduced the Th1/Th2 ratio of CD4 + T cells. Moreover, HIF-1α was predicted as a target gene of miR-18b-5p, which was further confirmed by dual-luciferase reporter assay, and HIF-1α was negatively associated with miR-18b-5p. Furthermore, overexpression of HIF-1α partially restored the effects of miR-18b-3p on inflammation and immunity in macrophages. Taken together, miR-18b-5p may be a novel therapeutic candidate target in splenic hemorrhagic shock treatment., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Hemorrhagic shock and trauma (HS/T)-induced gut injury may play a critical role in the development of multi-organ failure. Novel therapies that target gut injury and vascular permeability early after HS/T could have substantial impacts on trauma patients. In this study, we investigate the therapeutic potential of human mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC EVs) in vivo in HS/T in mice and in vitro in Caco-2 human intestinal epithelial cells., Methods: In vivo, using a mouse model of HS/T, vascular permeability to a 10-kDa dextran dye and histopathologic injury in the small intestine and lungs were measured among mice. Groups were (1) sham, (2) HS/T + lactated Ringer's (LR), (3) HS/T + MSCs, and (4) HS/T + MSC EVs. In vitro, Caco-2 cell monolayer integrity was evaluated by an epithelial cell impedance assay. Caco-2 cells were pretreated with control media, MSC conditioned media (CM), or MSC EVs, then challenged with hydrogen peroxide (H2O2)., Results: In vivo, both MSCs and MSC EVs significantly reduced vascular permeability in the small intestine (fluorescence units: sham, 456 ± 88; LR, 1067 ± 295; MSC, 765 ± 258; MSC EV, 715 ± 200) and lung (sham, 297 ± 155; LR, 791 ± 331; MSC, 331 ± 172; MSC EV, 303 ± 88). Histopathologic injury in the small intestine and lung was also attenuated by MSCs and MSC EVs. In vitro, MSC CM but not MSC EVs attenuated the increased permeability among Caco-2 cell monolayers challenged with H2O2., Conclusion: Mesenchymal stem cell EVs recapitulate the effects of MSCs in reducing vascular permeability and injury in the small intestine and lungs in vivo, suggesting MSC EVs may be a potential cell-free therapy targeting multi-organ dysfunction in HS/T. This is the first study to demonstrate that MSC EVs improve both gut and lung injury in an animal model of HS/T., (Copyright © 2021 American Association for the Surgery of Trauma.)

Background: Cell-based therapies using mesenchymal stem cell derived extracellular vesicles (EVs) improve neurologic outcomes in animal models of traumatic brain injury (TBI), stroke, and hemorrhage. Using a porcine 7-day survival model of TBI and hemorrhagic shock (HS), we previously demonstrated that EV-treatment was associated with reduced brain lesion size, neurologic severity score, and cerebral inflammation. However, the underlying cellular and genomic mechanisms remain poorly defined. We hypothesize that EV treatment modulates the brain transcriptome to enhance neuroprotection and neurorestoration following TBI + HS., Methods: Swine were subjected to severe TBI (8-mm cortical impact) and HS (40% blood volume). After 1 h of shock, animals were randomized (n = 4/group) to treatment with either lactated Ringer's (LR) or LR + EV. Both groups received fluid resuscitation after 2 h of shock, and autologous packed red blood cells 5 h later.After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data were imported into the iPathway pipeline for bioinformatics analyses., Results: 5,273 genes were differentially expressed in the LR + EV group versus LR alone (total 9,588 measured genes). Genes with the greatest upregulation were involved in synaptic transmission and neuronal development and differentiation, while downregulated genes were involved in inflammation. GO-terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed downregulation of inflammation, and upregulation of neurogenesis, and neuron survival and differentiation., Conclusions: In a porcine model of TBI + HS, EV treatment was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: The effect of resuscitative endovascular balloon occlusion of aorta (REBOA) in lowering mortality rate compared to resuscitative thoracotomy (RT) is inconclusive. In this updated systematic review and meta-analysis, we determined the effectiveness of the two techniques in patients with noncompressible torso hemorrhage (NCTH)., Materials and Methods: Online databases (PubMed, Embase, and MEDLINE) were searched until April 23, 2021, for original articles investigating the effect of REBOA on relevant outcomes (e.g., mortality in ED, mortality before discharge, in-hospital mortality, length of hospital stay and length of ICU stay) among NCTH patients in contrast to open aortic occlusion by RT. Data on baseline characteristics and endpoints were extracted. Review Manager version 5.4.1 and OpenMetaAnalyst were used for analyses. Risk ratios (RR) and the weighted mean differences (WMD) with corresponding 95% confidence intervals were calculated., Results: Eight studies were included having 3241 patients in total (REBOA: 1179 and RT: 2062). The pooled analysis demonstrated that compared to RT, mortality was significantly lower in the REBOA group in all settings: In emergency department (ED) (RR 0.63 [0.45, 0.87], P = 0.006, I 2  = 81%), before discharge (RR= 0.86 [0.75, 0.98], P = 0.03, I 2 = 93%), and in-hospital mortality (RR 0.80 [0.68, 0.95], P = 0.009, I 2 = 85%). Similarly, the length of ICU stay was significantly lower in REBOA group (WMD = 0.50 [-0.48, 1.48], P = 0.32, I 2 = 97%). However, no significant differences were observed in the length of hospital stay (WMD = 0.0 [-0.26, 0.26] P = 1)., Conclusions: Our pooled analysis shows REBOA to be effective in reducing mortality among NCTH patients. However, due to limited studies, the positive findings should be viewed discreetly and call for further investigation., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporize patients with infradiaphragmatic hemorrhage. Current guidelines advise < 30 min, to avoid ischemia/ reperfusion injury, whenever possible. The technique of partial REBOA (P-REBOA) has been developed to minimize the effects of distal ischemia. This study presents our clinical experience with P-REBOA, comparing outcomes to complete occlusion (C-REBOA)., Patients and Methods: Retrospective analysis of patients' electronic data and local REBOA registry between January 2016 and May 2019., Inclusion Criteria: adult trauma patients who received Zone I C-REBOA or P-REBOA for infradiaphragmatic hemorrhage, who underwent attempted exploration in the operating room. Comparison of outcomes based on REBOA technique (P-REBOA vs C-REBOA) and occlusion time (> 30 min, vs ≤ 30 min) RESULTS: 46 patients were included, with 14 treated with P-REBOA. There were no demographic differences between P-REBOA and C-REBOA. Prolonged (> 30 min) REBOA (regardless of type of occlusion) was associated with increased mortality (32% vs 0%, p = 0.044) and organ failure. When comparing prolonged P-REBOA with C-REBOA, there was a trend toward lower ventilator days [19 (11) vs 6 (9); p = 0.483] and dialysis (36.4% vs 16.7%; p = 0.228) with significantly less vasopressor requirement (72.7% vs 33.3%; p = 0.026)., Conclusion: P-REBOA can be delivered in a clinical setting, but is not currently associated with improved survival in prolonged occlusion. In survivors, there is a trend toward lower organ support needs, suggesting that the technique might help to mitigate ischemic organ injury. More clinical data are needed to clarify the benefit of partial occlusion REBOA., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The purpose of this study was to evaluate the current management and clinical outcomes in patients with hemodynamic instability due to pelvic fracture in three regional trauma centres in Korea., Patients and Methods: Three regional trauma centres participated in this study, and 157 patients who were admitted between January 2015 and December 2018 were enroled. Clinical data were collected prospectively as part of the Korean trauma data bank and were analysed retrospectively., Results: The mean age was 59.3 years, and 107 of 157 (68.2%) were male patients. The most common cause of injury was auto-pedestrian accidents, followed by falls and motor vehicle crashes. The mean admission systolic blood pressure and serum lactate level were 86.7 mmHg and 6.68 mmol/L, respectively. Twenty-four patients (15.3%) had a cardiac arrest in the emergency department (ED). The mean injury severity score was 39.1, and the mean probability of survival (Trauma and Injury Severity Score) was 48.7%. Sixty-six patients (42%) underwent pelvic angiography; 89 (56.7%), preperitoneal pelvic packing (PPP); 27 (17.2%), resuscitative endovascular balloon occlusion of the aorta (REBOA); 20 (12.7%), pelvic external fixation (PEF); and 13 patients (8.3%), internal iliac artery ligation (IIAL). Seventy-three patients (46.5%) died, including 40 (25.5%) who died from acute haemorrhage. With each year, the rates of REBOA and pelvic binder use continued to increase (p<0.001 and p = 0.005, respectively), but the number of PEF cases significantly decreased (p = 0.006). Age, initial lactate, low revised trauma score (RTS), combined abdominal injury, REBOA, and 4-hour requirement of packed red blood cells were independent risk factors associated with mortality, whereas during the period of 2017 and 2018, there were protective factors. The risk factors of mortality due to haemorrhage were cardiac arrest in the ED, RTS, combined chest and abdominal injuries, and IIAL., Conclusions: Since the establishment of regional trauma centres, the clinical outcomes of patients with hemodynamic instability due to pelvic fracture have significantly improved. As a haemostatic procedure for these patients, PEF has been used less frequently, while pelvic binder and REBOA showed significant increase in their use., Competing Interests: Declaration of Competing Interests All authors have no conflict of interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The data on resuscitative endovascular balloon occlusion of the aorta (REBOA) use continue to grow with its increasing use in trauma centers. The data in her last 5 years have not been systematically reviewed. We aim to assess current literature related to REBOA use and outcomes among civilian trauma populations., Methods: A literature search using PubMed, EMBASE, and JAMA Network for studies regarding REBOA usage in civilian trauma from 2016 to 2020 is carried out. This review followed preferred reporting items for systematic reviews and meta-analysis guidelines., Results: Our search yielded 35 studies for inclusion in our systematic review, involving 4073 patients. The most common indication for REBOA was patient presentation in hemorrhagic shock secondary to traumatic injury. REBOA was associated with significant systolic blood pressure improvement. Of 4 studies comparing REBOA to non-REBOA controls, 2 found significant mortality benefit with REBOA. Significant mortality improvement with REBOA compared to open aortic occlusion was seen in 4 studies. In the few studies investigating zone placement, highest survival rate was seen in patients undergoing zone 3. Overall, reports of complications directly related to overall REBOA use were relatively low., Conclusion: REBOA has been shown to be effective in promoting hemodynamic stability in civilian trauma. Mortality data on REBOA use are conflicting, but most studies investigating REBOA vs. open occlusion methods suggest a significant survival advantage. Recent data on the REBOA technique (zone placement and partial REBOA) are sparse and currently insufficient to determine advantage with any particular variation. Overall, larger prospective civilian trauma studies are needed to better understand the benefits of REBOA in high-mortality civilian trauma populations., Study Type: Systematic Review., Level of Evidence: III- Therapeutic.

Background: Hemodynamic instability due to torso hemorrhage can be managed with the assistance of resuscitative endovascular balloon occlusion of the aorta (REBOA). This is a report of a single-center experience using the ER-REBOA™ catheter for traumatic and non-traumatic cases as an adjunct to hemorrhage control and as part of the EndoVascular resuscitation and Trauma Management (EVTM) concept. The objective of this report is to describe the clinical usage, technical success, results, complications and outcomes of the ER-REBOA™ catheter at Örebro University hospital, a middle-sized university hospital in Europe., Methods: Data concerning patients receiving the ER-REBOA™ catheter for any type of hemorrhagic shock and hemodynamic instability at Örebro University hospital in Sweden were collected prospectively from October 2015 to May 2020., Results: A total of 24 patients received the ER-REBOA™ catheter (with the intention to use) for traumatic and non-traumatic hemodynamic control; it was used in 22 patients. REBOA was performed or supervised by vascular surgeons using 7-8 Fr sheaths with an anatomic landmark or ultrasound guidance. Systolic blood pressure (SBP) increased significantly from 50 mmHg (0-63) to 95 mmHg (70-121) post REBOA. In this cohort, distal embolization and balloon rupture due to atherosclerosis were reported in one patient and two patients developed renal failure. There were no cases of balloon migration. Overall 30-day survival was 59%, with 45% for trauma patients and 73% for non-traumatic patients. Responders to REBOA had a significantly lower rate of mortality at both 24 h and 30 days., Conclusions: Our clinical data and experience show that the ER-REBOA™ catheter can be used for control of hemodynamic instability and to significantly increase SBP in both traumatic and non-traumatic cases, with relatively few complications. Responders to REBOA have a significantly lower rate of mortality., (© 2021. The Author(s).)

Purpose: In the past decade blast injuries have become more prevalent. Blast trauma may cause extensive injuries requiring improved early resuscitation and prevention of haemorrhage. Randomized prospective trials are logistically and ethically challenging, and large animal models are important for further research efforts. Few severe blast trauma models have been described, which is why we aimed to establish a comprehensive polytrauma model in accordance with the criteria of the Berlin definition of polytrauma and with a survival time of > 2 h. Multiple blast injuries to the groin and abdomen were combined with hypoperfusion, respiratory and metabolic acidosis, hypoventilation, hypothermia and inflammatory response. The model was compared to lung contusion and haemorrhage., Methods: 16 landrace swine (mean weight 60.5 kg) were randomized to "control" (n = 5), "chest trauma/hem" by lung contusion and class II haemorrhage (n = 5), and "blast polytrauma" caused by multiple blast injuries to the groin and abdomen, class II haemorrhage, lipopolysaccharide (LPS) infusion and hypothermia 32 °C (n = 6)., Results: The blast polytrauma group had an Injury Severity Score of 57 which resulted in haemodynamic shock, hypothermia, respiratory and metabolic acidosis and inflammatory response. The chest trauma/hem group had an Injury Severity Score of 9 and less profound physiologic effects. Physiologic parameters presented a dose-response relationship corresponding to the trauma levels., Conclusion: A comprehensive blast polytrauma model fulfilling the Berlin polytrauma criteria, with a high trauma load and a survival time of > 2 h was established. A severe, but consistent, injury profile was accomplished enabling the addition of experimental interventions in future studies, particularly of immediate resuscitation efforts including whole blood administration, trauma packing and haemostasis., (© 2020. The Author(s).)

Abstract: Excessive sympathetic outflow following trauma can lead to cardiac dysfunction, inflammation, coagulopathy, and poor outcomes. We previously reported that buprenorphine analgesia decreased survival after hemorrhagic trauma. Our aim is to examine the underlying mechanisms of mortality in a non-compressible hemorrhage rat model resuscitated with saline or adenosine, lidocaine, magnesium (ALM). Anesthetized adult male Sprague-Dawley rats were randomly assigned to Saline control group or ALM therapy group (both n = 10). Hemorrhage was induced by 50% liver resection. After 15 min, 0.7 mL/kg 3% NaCl ± ALM intravenous bolus was administered, and after 60 min, 0.9% NaCl ± ALM was infused for 4 h (0.5 mL/kg/h) with 72 h monitoring. Animals received 6-12-hourly buprenorphine for analgesia. Hemodynamics, heart rate variability, echocardiography, and adiponectin were measured. Cardiac tissue was analyzed for adrenergic/cholinergic receptor expression, inflammation, and histopathology. Four ALM animals and one Saline control survived to 72 h. Mortality was associated with up to 97% decreases in adrenergic (β-1, α-1A) and cholinergic (M2) receptor expression, cardiac inflammation, myocyte Ca2+ loading, and histopathology, indicating heart ischemia/failure. ALM survivors had higher cardiac output and stroke volume, a 30-fold increase in parasympathetic/sympathetic receptor expression ratio, and higher circulating adiponectin compared to Saline controls. Paradoxically, Saline cardiac adiponectin hormone levels were higher than ALM, with no change in receptor expression, indicating intra-cardiac synthesis. Mortality appears to be a "systems failure" associated with CNS dysregulation of cardiac function. Survival involves an increased parasympathetic dominance to support cardiac pump function with reduced myocardial inflammation. Increased cardiac α-1A adrenergic receptor in ALM survivors may be significant, as this receptor is highly protective during heart dysfunction/failure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Purpose: Pelvic and lower junctional hemorrhage result in a significant amount of trauma related deaths in military and rural civilian environments. The Abdominal Aortic and Junctional Tourniquet (AAJT) and infra-renal (zone 3) Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) are two options for resuscitation of patients with life threatening blood loss from and distal to the pelvis. Evidence suggest differences in the hemodynamic response between AAJT and zone 3 REBOA, but fluid management during resuscitation with the devices has not been fully elucidated. We compared crystalloid fluid requirements (Ringer's acetate) between these devices to maintain a carotid mean arterial pressure (MAP) > 60 mmHg., Methods: 60 kg anesthetized and mechanically ventilated male pigs were subjected to a mean 1030 (range 900-1246) mL (25% of estimated total blood volume, class II) haemorrhage. AAJT (n = 6) or zone 3 REBOA (n = 6) were then applied for 240 min. Crystalloid fluids were administered to maintain carotid MAP. The animals were monitored for 30 min after reperfusion., Results: Cumulative resuscitative fluid requirements increased 7.2 times (mean difference 2079 mL; 95% CI 627-3530 mL) in zone 3 REBOA (mean 2412; range 800-4871 mL) compared to AAJT (mean 333; range 0-1000 mL) to maintain target carotid MAP. Release of the AAJT required vasopressor support with norepinephrine infusion for a mean 9.6 min (0.1 µg/kg/min), while REBOA release required no vasopressor support., Conclusion: Zone 3 REBOA required 7.2 times more crystalloids to maintain the targeted MAP. The AAJT may therefore be considered in a situation of hemorrhagic shock to limit the need for crystalloid infusions, although removal of the AAJT caused more severe hemodynamic and metabolic effects which required vasopressor support., (© 2021. The Author(s).)

Background: Deviation from guidelines is frequent in emergency situations, and this may lead to increased mortality. Probably because of time constraints, 55% is the greatest reported guidelines compliance rate in severe trauma patients. This study aimed to identify among all available recommendations a reasonable bundle of items that should be followed to optimize the outcome of hemorrhagic shocks (HSs) and severe traumatic brain injuries (TBIs)., Methods: We first estimated the compliance with French and European guidelines using the data from the French TraumaBase registry. Then, we used a machine learning procedure to reduce the number of recommendations into a minimal set of items to be followed to minimize 7-day mortality. We evaluated the bundles using an external validation cohort., Results: This study included 5,924 trauma patients (1,414 HS and 4,955 TBI) between 2011 and August 2019 and studied compliance to 36 recommendation items. Overall compliance rate to recommendation items was 71.6% and 66.9% for HS and TBI, respectively. In HS, compliance was significantly associated with 7-day decreased mortality in univariate analysis but not in multivariate analysis (risk ratio [RR], 0.91; 95% confidence interval [CI], 0.90-1.17; p = 0.06). In TBI, compliance was significantly associated with decreased mortality in univariate and multivariate analysis (RR, 0.85; 95% CI, 0.75-0.92; p = 0.01). For HS, the bundle included 13 recommendation items. In the validation cohort, when this bundle was applied, patients were found to have a lower 7-day mortality rate (RR, 0.46; 95% CI, 0.27-0.63; p = 0.01). In TBI, the bundle included seven items. In the validation cohort, when this bundle was applied, patients had a lower 7-day mortality rate (RR, 0.55; 95% CI, 0.34-0.71; p = 0.02)., Discussion: Using a machine-learning procedure, we were able to identify a subset of recommendations that minimizes 7-day mortality following traumatic HS and TBI. These two bundles remain to be evaluated in a prospective manner., Level of Evidence: Care Management, level II., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sodium thiosulfate (Na2S2O3) is a clinically established drug with antioxidant and sulphide-releasing properties. Na2S2O3 mediated neuro- and cardioprotective effects in ischemia/reperfusion models and anti-inflammatory effects in LPS-induced acute lung injury. Moreover, Na2S2O3 improved lung function during resuscitation from hemorrhagic shock in swine with pre-existing atherosclerosis, characterized by decreased expression of cystathionine γ-lyase (CSE), a major source of hydrogen sulfide (H2S) synthesis in the vasculature. Based on these findings, we investigated the effects of Na2S2O3 administration during resuscitation from trauma-and-hemorrhage in mice under conditions of whole body CSE deficit., Methods: After blast wave-induced blunt chest trauma and surgical instrumentation, CSE knockout (CSE-/-) mice underwent 1 h of hemorrhagic shock (MAP 35 ± 5 mm Hg). At the beginning of resuscitation comprising retransfusion, norepinephrine support and lung-protective mechanical ventilation, animals received either i.v. Na2S2O3 (0.45 mg g-1, n = 12) or vehicle (saline, n = 13). Hemodynamics, acid-base status, metabolism using stable isotopes, and visceral organ function were assessed. Blood and organs were collected for analysis of cytokines, mitochondrial respiratory capacity, and immunoblotting., Results: Na2S2O3 treatment improved arterial paO2 (P = 0.03) coinciding with higher lung tissue glucocorticoid receptor expression. Norepinephrine requirements were lower in the Na2S2O3 group (P < 0.05), which was associated with lower endogenous glucose production and higher urine output. Na2S2O3 significantly increased renal tissue IκBα and heme oxygenase-1 expression, whereas it lowered kidney IL-6 and MCP-1 levels., Conclusion: Na2S2O3 exerted beneficial effects during resuscitation of murine trauma-and-hemorrhage in CSE-/- mice, confirming and extending the previously described organ-protective and anti-inflammatory properties of Na2S2O3. The findings make Na2S2O3 a potentially promising therapeutic option in the context of impaired CSE activity and/or reduced endogenous H2S availability., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Introduction: Uncontrolled bleeding is the primary cause of death in complex liver trauma and perihepatic packing is regularly utilized for hemorrhage control. The purpose of this study was to investigate the effectiveness of a novel inflatable device (the airbag) for perihepatic packing using a validated liver injury damage control model in swine., Material and Methods: The image of the human liver was digitally isolated within an abdominal computerized tomography scan to produce a silicone model of the liver to mold the airbag. Two medical grade polyurethane sheets were thermal bonded to the configuration of the liver avoiding compression of the hepatic pedicle, hepatic veins, and the suprahepatic vena cava after inflation. Yorkshire pigs (n = 22) underwent controlled hemorrhagic shock (35% of the total blood volume), hypothermia, and fluid resuscitation to reproduce the indications for damage control surgery (coagulopathy, hypothermia, and acidosis) prior to a liver injury. A 3 × 10 cm rectangular segment of the left middle lobe of the liver was removed to create the injury. Subsequently, the animals were randomized into 4 groups for liver damage control (240 min), Sponge Pack (n = 6), Pressurized Airbag (n = 6), Vacuum Airbag (n = 6), and Uncontrolled (n = 4). Animals were monitored throughout the experiment and blood samples obtained., Results: Perihepatic packing with the pressurized airbag led to significantly higher mean arterial pressure during the liver damage control phase compared to sponge pack and vacuum airbag 52 mmHg (SD 2.3), 44.9 mmHg (SD 2.1), and 32 mmHg (SD 2.3), respectively (p < 0.0001), ejection fraction was also higher in that group. Hepatic hemorrhage was significantly lower in the pressurized airbag group compared to sponge pack, vacuum airbag, and uncontrolled groups; respectively 225 ml (SD 160), 611 ml (SD 123), 991 ml (SD 385), 1162 ml (SD 137) (p < 0001). Rebleeding after perihepatic packing removal was also significantly lower in the pressurized airbag group; respectively 32 ml (SD 47), 630 ml (SD 185), 513 ml (SD 303), (p = 0.0004). Intra-abdominal pressure remained similar to baseline, 1.9 mmHg (SD 1), (p = 0.297). Histopathology showed less necrosis at the border of the liver injury site with the pressurized airbag., Conclusion: The pressurized airbag was significantly more effective at controlling hepatic hemorrhage and improving hemodynamics than the traditional sponge pack technique. Rebleeding after perihepatic packing removal was negligible with the pressurized airbag and it did not provoke hepatic injury., Competing Interests: Declaration of Competing Interest Dr. Joao Rezende-Neto MD, PhD, was the inventor of the Liver Airbag Device and has filed a patent. Patent Cooperation Treaty (PCT/CA/2019/050345). Sachin Doshi MD, M.Eng, David Gomez MD, PhD, Bruna Camilotti MD, Dan Marcuzzi BSc, MD, Andrew Beckett CD, MD. Have no conflicts to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Hemorrhagic shock in horses may be classified in several ways. Hemorrhage may be considered internal versus external, controlled or uncontrolled, or described based on the severity of hypovolemic shock the patient is experiencing. Regardless of the cause, as the severity of hemorrhage worsens, homeostatic responses are stimulated to ameliorate the systemic and local effects of an oxygen debt. In mild to moderate cases of hemorrhage (<15% blood volume loss), physiological adaptations in the patient may not be clinically apparent. As hemorrhage worsens, often in the uncontrolled situation such as a vascular breach internally, the pathophysiological consequences are numerous. The patient mobilizes fluid and reserve blood volume, notably splenic stored and peripherally circulating erythrocytes, to preferentially supply oxygen to sensitive organs such as the brain and heart. When the global and local delivery of oxygen is insufficient to meet the metabolic needs of the tissues, a cascade of cellular, tissue, and organ dysfunction occurs. If left untreated, the patient dies of hemorrhagic anemic shock., Clinical Importance: An understanding of the pathophysiological consequences of hemorrhagic shock in horses and their clinical manifestations may help the practitioner understand the severity of blood volume loss, the need for referral, the need for transfusion, and potential outcome. In cases of severe acute uncontrolled hemorrhage, it is essential to recognize the clinical manifestations quickly to best treat the patient, which may include humane euthanasia., Key Points: Uncontrolled hemorrhage may be defined as the development of a vascular breach and hemorrhage that cannot be controlled by interventional hemostasis methods such as external pressure, tourniquet, or ligation. Causes of uncontrolled hemorrhage in horses may be due to non-surgical trauma, surgical trauma, invasive diagnostic procedures including percutaneous organ biopsy, coagulopathy, hypertension, cardiovascular anomaly, vascular damage, neoplasia such as hemangiosarcoma, toxicity, or idiopathic in nature. When a critical volume of blood is lost, the respondent changes in heart rate, splenic blood mobilization, and microcirculatory control can no longer compensate for decreasing oxygen delivery to the tissues In spite of organ-specific microvascular responses (eg, myogenic responses, local mediator modulation of microvasculature, etc), all organs experience decreases in blood flow during severe hypovolemia Acute, fatal hemorrhagic shock is characterized by progressive metabolic acidosis, coagulopathy, and hypothermia, often termed the "triad of death," followed by circulatory collapse., (© Veterinary Emergency and Critical Care Society 2022.)

Background: The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight., Methods: An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes., Results: Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1β was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR., Conclusion: Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies., (Copyright © 2021 American Association for the Surgery of Trauma.)

Background: Although the resuscitation of an adult trauma patient has been researched and written about for the past century, the ideal fluid strategy to infuse during the initial resuscitation period remains unresolved. This work was aimed at assessing the effect of hypotensive versus conventional resuscitation strategies in traumatic hemorrhagic shock patients on mortality, and the need for blood transfusions including adverse events., Methods: This systematic review and meta-analysis were performed following the PRISMA guidelines. Electronic databases were searched for randomized controlled trials (RCT) comparing the effect of hypotension versus conventional fluid resuscitation for traumatic hemorrhagic shock patients. Two reviewers independently performed the screening, data extraction, and bias assessment. The data analysis was completed using the Cochrane Collaboration's software RevMan 5.4., Results: Data from 28 RCTs on 4503 patients were included in the final meta-analysis. Patients receiving hypotension fluid resuscitation compared with conventional fluid resuscitation experienced less mortality (12.5% vs. 21.4%; RR = 0.58; 95% CI: 0.51-0.66; p < 0.001), fewer adverse events (10.8% vs. 13.4%; RR = 0.70; 95% CI: 0.59-0.83; p < 0.001), including fever acute respiratory distress syndrome (7.8% vs. 16.8%) or multiple organ dysfunction syndrome (8.6% vs. 21.6%)., Conclusions: This meta-analysis showed that hypotensive fluid resuscitation significantly reduced the mortality of hypovolemic shock patients. Findings are low in certainty and should be interpreted with caution. Therefore, there is an urgent need for larger, multicenter, randomized trials to confirm these findings.

Background: Trauma is the leading cause of pediatric mortality in the United States. Often, these patients require supermassive transfusion (SMT), which we define as receipt of >80 mL/kg blood products, double the proposed volume for standard pediatric massive transfusion (MT). Evaluating the blood volumes, injury patterns, clinical findings, and prehospital interventions predictive for SMT are critical to reducing pediatric mortality. We describe the pediatric casualties, injury patterns, and clinical findings that comprise SMT., Methods: We retrospectively analyzed pediatric trauma data from the Department of Defense Trauma Registry from January 2007-2016. We stratified patients into two cohorts based on blood products received in the first 24 h after injury: 1) those who received 40-80 mL/kg (MT), or 2) those who received >80 mL/kg (SMT). We evaluated demographics, injury patterns, prehospital interventions, and clinical findings., Results: Our original dataset included 3439 pediatric casualties. We identified 536 patients who met inclusion parameters (receipt of ≥40 mL/kg of blood products [whole blood, packed red blood cells, fresh frozen plasma, platelets, or cryoprecipitate]). The MT cohort included 271 patients (50.6%), and the SMT cohort comprised 265 patients (49.4%). Survival to discharge was significantly lower (78% for SMT, 86% for MT; p < 0.011) in the SMT cohort. Multivariable analysis of injury patterns revealed serious injuries (Abbreviated Injury Scale 3-6) to the extremities (OR 2.13, 95% CI 1.45-3.12) and abdomen (OR 1.65, 1.08-2.53) were associated with SMT. Wound dressings (41% versus 29%; p = 0.003), tourniquets (23% vs 12%; p = 0.001), and IO access (17% vs 10%; p = 0.013) were more common in the SMT group. Age-adjusted hypotension was significantly higher in the SMT group (41%, n = 100 vs 23%, n = 59; p < 0.001) with no statistical difference detected in tachycardia (87%, n = 223 vs 87%, n = 228; p = 0.932)., Conclusions: Our research demonstrates that pediatric SMT patients are at increased risk of mortality. Our study highlights the seriousness of extremity injuries in pediatric trauma patients, identifying associations between severe injuries to the extremities and abdomen with the receipt of SMT. Prehospital interventions of wound dressing, tourniquets, and IO access were more frequent in the SMT cohort. Our research determined that hypotension was associated with SMT, but tachycardia was not a reliable predictor of SMT over MT., Competing Interests: Declaration of Competing Interest We have no conflicts to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hemorrhagic shock is a common condition that may lead to hemodynamic instability, decreased oxygen delivery, cellular hypoxia, organ damage, and ultimately death., Clinical Importance: This review addresses the pathophysiology of hemorrhagic shock. Hemorrhagic shock can be rapidly fatal and is the leading cause of death in human trauma patients. Understanding the pathophysiology of hemorrhagic shock is imperative in understanding the current hemostatic and resuscitative strategies and is foundational to the development of new therapeutic options., Key Points: Shock is a state of inadequate cellular energy production and can be triggered by many causes Both traumatic and non-traumatic causes of hemorrhage can lead to the development of hemorrhagic shock Prompt recognition and attenuation of hemorrhage is paramount in preventing the onset or potentiation of hemorrhagic shock Acute hemorrhage produces distinct physiological responses depending on the magnitude and rate of hemorrhage. Hemorrhagic shock may be directly related to the initial injury but may also be exacerbated and complicated by a post-traumatic coagulopathy, termed acute traumatic coagulopathy., (© Veterinary Emergency and Critical Care Society 2022.)

Resuscitative endovascular balloon occlusion of the aorta (REBOA) for rapid hemorrhage control is increasingly being used in trauma management. Its beneficial hemodynamic effects on unstable patients beyond temporal hemostasis has led to growing interest in its use in other patient populations, such as during cardiac arrest from nontraumatic causes. The ability to insert the catheters without fluoroscopic guidance makes the technique available in the prehospital setting. However, in addition to correct positioning, challenges include reliably achieving aortic occlusion while minimizing the risk of balloon rupture. Without fluoroscopic control, inflation of the balloon relies on estimated aortic diameters and on the disappearing pulse in the contralateral femoral artery. In the case of cardiac arrest or absent palpable pulses, balloon inflation is associated with excess risk of overinflation and adverse events (vessel damage, balloon rupture). In this bench study, we examined how the pressure in the balloon is related to the surrounding blood pressure and the balloon's contact with the vessel wall in two sets of experiments, including a pulsatile circulation model. With this data, we developed a rule of thumb to guide balloon inflation of the ER-REBOA catheter with a simple disposable pressure-reading device (COMPASS). We recommend slowly filling the balloon with saline until the measured balloon pressure is 160 mmHg, or 16 mL of saline have been used. If after 16 mL the balloon pressure is still below 160 mmHg, saline should be added in 1-mL increments, which increases the pressure target about 10 mmHg at each step, until the maximum balloon pressure is reached at 240 mmHg (= 24 mL inflation volume). A balloon pressure greater than 250 mmHg indicates overinflation. With this rule and a disposable pressure-reading device (COMPASS), ER-REBOA balloons can be safely filled in austere environments where fluoroscopy is unavailable. Pressure monitoring of the balloon allows for recognition of unintended deflation or rupture of the balloon., (© 2021. The Author(s).)

Improved surgical outcomes have been achieved as a result of preoperative risk assessments and developments in surgical and anaesthetic techniques. However, post-operative haemorrhage remains a life-threatening complication requiring swift recognition and management. This article explores the compensatory mechanisms the body employs during haemorrhage and how these may present as altered observations that can aid early recognition. It also describes the rapid assessment of patients using the ABCDE (airway, breathing, circulation, disability, exposure) approach and outlines the management interventions used to halt the bleeding and restore intravascular volume., Competing Interests: None declared, (© 2021 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Introduction: Exsanguination remains a leading cause of preventable death in traumatically injured patients. To better treat hemorrhagic shock, hospitals have adopted massive transfusion protocols (MTPs) which accelerate the delivery of blood products to patients. There has been an increase in mass casualty events (MCE) worldwide over the past two decades. These events can overwhelm a responding hospital's supply of blood products. Using a computerized model, this study investigated the ability of US trauma centers (TCs) to meet the blood product requirements of MCEs., Methods: Cross-sectional survey data of on-hand blood products were collected from 16 US level-1 TCs. A discrete event simulation model of a TC was developed based on historic data of blood product consumption during MCEs. Each hospital's blood bank was evaluated across increasingly more demanding MCEs using modern MTPs to guide resuscitation efforts in massive transfusion (MT) patients., Results: A total of 9,000 simulations were performed on each TC's data. Under the least demanding MCE scenario, the median size MCE in which TCs failed to adequately meet blood product demand was 50 patients (IQR 20-90), considering platelets. Ten TCs exhaust their supply of platelets prior to red blood cells (RBCs) or plasma. Disregarding platelets, five TCs exhausted their supply of O- packed RBCs, six exhausted their AB plasma supply, and five had a mixed exhaustion picture., Conclusion: Assuming a TC's ability to treat patients is limited only by their supply of blood products, US level-1 TCs lack the on-hand blood products required to adequately treat patients following a MCE. Use of non-traditional blood products, which have a longer shelf life, may allow TCs to better meet the blood product requirement needs of patients following larger MCEs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Purpose: Non-compressible torso hemorrhage is a major but potentially preventable cause of trauma-related mortality. REBOA has rapidly emerged as an adjunct for hemorrhage control. However, little is known about the proportion of trauma patients in which REBOA may be indicated. The aim of our study was to determine this proportion., Methods: A retrospective cohort study of all adult (≥ 16 years) trauma patients treated at our facility (a university hospital and trauma referral center covering 2.5 million inhabitants) between 2012 and 2017 was performed. Potential candidates for REBOA were patients with an abdominal and/or pelvic injury and an Abbreviated Injury Scale (AIS) score of ≥ 3, who arrived in shock (defined as a systolic blood pressure, SBP ≤ 90 mmHg). Patients with potential contraindication for REBOA (prehospital cardiac arrest or thoracic vascular injury) were excluded., Results: From a total of 7229 patients during the study years, 31 (0.4%) patients met the criteria for potential use of REBOA. In this cohort, the total mortality was 45% and the mortality within 30 days was 26%. The mean Injury Severity Score (ISS) was 46.3 and mean SBP was 72 mmHg., Conclusions: The study suggests a potential indication for REBOA (incidence) of 2.5 per one million inhabitants per year according to the used criteria. Local REBOA guidelines may vary but a significant number of trauma centers use similar criteria. Although the total mortality within this group is high, the number of patients that theoretically may benefit from the use of REBOA is low., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Prehospital plasma transfusion is lifesaving for trauma patients in hemorrhagic shock but is not commonly used owing to cost and feasibility concerns., Objective: To evaluate the cost-effectiveness of prehospital thawed plasma transfusion in trauma patients with hemorrhagic shock during air medical transport., Design, Setting, and Participants: A decision tree and Markov model were created to compare standard care and prehospital thawed plasma transfusion using published and unpublished patient-level data from the Prehospital Plasma in Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock (PAMPer) trial conducted from May 2014 to October 2017, health care and trauma-specific databases, and the published literature. Prehospital transfusion, short-term inpatient care, and lifetime health care costs and quality of life outcomes were included. One-way, 2-way, and Monte Carlo probabilistic sensitivity analyses were performed across clinically plausible ranges. Data were analyzed in December 2019., Main Outcomes and Measures: Relative costs and health-related quality of life were evaluated by an incremental cost-effectiveness ratio at a standard willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY)., Results: The trial included 501 patients in the modified intention-to-treat cohort. Median (interquartile range) age for patients in the thawed plasma and standard care cohorts were 44 (31-59) and 46 (28-60) years, respectively. Overall, 364 patients (72.7%) were male. Thawed plasma transfusion was cost-effective with an incremental cost-effectiveness ratio of $50 467.44 per QALY compared with standard care. The preference for thawed plasma was robust across all 1- and 2-way sensitivity analyses. When considering only patients injured by a blunt mechanism, the incremental cost-effectiveness ratio decreased to $37 735.19 per QALY. Thawed plasma was preferred in 8140 of 10 000 iterations (81.4%) on probabilistic sensitivity analysis. A detailed analysis of incremental costs between strategies revealed most were attributable to the in-hospital and postdischarge lifetime care of critically ill patients surviving severe trauma., Conclusions and Relevance: In this study, prehospital thawed plasma transfusion during air medical transport for trauma patients in hemorrhagic shock was lifesaving and cost-effective compared with standard care and should become commonplace.

Abstract: Mortality secondary to trauma-related hemorrhagic shock has not improved for several decades. Underlying the stall in progress is the conundrum of effective prehospital interventions for hemorrhage control. As we know, neither pressing hard on the gas nor "stay and play" has changed mortality over the last 20 years. For this reason, when dealing with effective changes that will improve severe hemorrhage mortality outcomes, there is a need for the creation of a hybrid prehospital model. Improvements in mortality outcomes for patients with severe hemorrhage based on evidence for common civilian prehospital procedures such as in-field intubation and immediate fluid resuscitation with crystalloid solution are weak at best. The use of tourniquets, once considered too risky to use, however, has risen dramatically in large part due to success seen during their use in the military. Their use in the civilian setting shows promising results. Recently updated military Advanced Resuscitative Care guidelines propose the use of prehospital whole blood transfusion as well as in-field use of Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta. Several case studies from Europe suggest these strategies are feasible for use in the civilian population, but could they be implemented in the US?, Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)