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Trauma-related hemorrhagic shock (HS) remains a leading cause of death among military and civilian trauma patients. We have previously shown that administration of complement and HMGB1 inhibitors attenuate morbidity and mortality 24 h after injury in a rat model of blast injury (BI) and HS. To further validate these results, this study aimed to develop a swine model and evaluate BI+HS-induced pathophysiology. Anesthetized Yucatan minipigs underwent combined BI and volume-controlled hemorrhage. After 30 min of shock, animals received an intravenous bolus of PlasmaLyte A and a continuous PlasmaLyte A infusion. The survival rate was 80% (4/5), and the non-survivor expired 72 min post-BI. Circulating organ-functional biomarkers, inflammatory biomarkers, histopathological evaluation, and CT scans indicated evidence of multiple-organ damage, systemic innate immunological activation, and local tissue inflammation in the injured animals. Interestingly, a rapid and dramatic increase in plasma levels of HMGB1 and C3a and markedly early myocarditis and encephalitis were associated with early death post-BI+HS. This study suggests that this model reflects the immunopathological alterations of polytrauma in humans during shock and prolonged damage control resuscitation. This experimental protocol could be helpful in the assessment of immunological damage control resuscitation approaches during the prolonged care of warfighters.

Severe physical injuries and associated traumatic brain injury and/or hemorrhagic shock (HS) remain leading causes of death worldwide, aggravated by accompanying extensive inflammation. Retrospective clinical data indicated an association between mild hyperoxemia and improved survival and outcome. However, corresponding prospective clinical data, including long-term resuscutation, are scarce. Therefore, the present study explored the effect of mild hyperoxemia for 24 hours in a prospective randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma (ASDH) and HS. ASDH was induced by injecting 0.1 ml × kg -1 autologous blood into the subdural space and HS was triggered by passive removal of blood. After 2 hours, the animals received full resuscitation, including retransfusion of the shed blood and vasopressor support. During the first 24 hours, the animals underwent targeted hyperoxemia (P a O 2 = 200 - 250 mmHg) or normoxemia (P a O 2 = 80 - 120 mmHg) with a total observation period of 55 hours after the initiation of ASDH and HS. Survival, cardiocirculatory stability, and demand for vasopressor support were comparable between both groups. Likewise, humoral markers of brain injury and systemic inflammation were similar. Multimodal brain monitoring, including microdialysis and partial pressure of O 2 in brain tissue, did not show significant differences either, despite a significantly better outcome regarding the modified Glasgow Coma Scale 24 hours after shock that favors hyperoxemia. In summary, the present study reports no deleterious and few beneficial effects of mild targeted hyperoxemia in a clinically relevant model of ASDH and HS with long-term resuscitation in otherwise healthy pigs. Further beneficial effects on neurological function were probably missed due to the high mortality in both experimental groups. The present study remains exploratory due to the unavailability of an a priori power calculation resulting from the lack of necessary data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023 Datzmann, Münz, Hoffmann, Moehrke, Binzenhöfer, Gröger, Kapapa, Mathieu, Mayer, Zink, Gässler, Wolfschmitt, Hogg, Merz, Calzia, Radermacher and Messerer.)

Introduction: Marine casualties are increasing, and mortality from trauma associated with immersion in seawater is high. However, the associated pathophysiological characteristics remain unclear, limiting research into the early emergency treatment strategy., Methods: Healthy and 50% hemorrhagic shock rats were soaked in 15°C and 21°C seawater for 2 h, 4 h and 6 h, respectively, and the effects on vital signs, internal environment, tissue metabolism, lethal triad, vital organ functions and survival were observed., Results: Immersion in seawater can cause death in healthy rats. Rats with hemorrhagic shock in 15°C seawater showed a lower survival rate than the corresponding groups in 21°C seawater. Moreover, compared with 21°C seawater, 15°C seawater played a more remarkable role in decreasing mean arterial pressure, heart rate, and respiration rate, increasing water content and decreasing Na + /K + -ATPase activity in the brain and lung; increase in plasma osmolality, Na + , K + , Cl - , and the occurrence of the lethal triad manifested by a decrease in core body temperature, pH, lactate, and an increase in coagulation parameters, as well as damage to cardiac, intestinal, hepatic, and renal functions in rats with hemorrhagic shock., Conclusions: Immersion in seawater at low temperatures could be lethal to healthy rats, causing the occurrence of a lethal triad and damage to vital organs. Furthermore, 15°C-seawater had a more significant effect than 21°C-seawater on aggravating the imbalance of internal environment and tissue metabolism, resulting in a higher incidence of the lethal triad and thus aggravating the dysfunctions of vital organs, which eventually resulted in higher mortality in rats with hemorrhagic shock., (Copyright © 2022. Published by Elsevier Inc.)

Background: The recent pandemic exposed a largely unrecognized threat to medical resources, including daily available blood products. Some of the most severely injured patients who arrive in extremis consume tremendous resources yet succumb shortly after arrival. We sought to identify cut points available early in the patient's resuscitation that predicted 100% mortality., Study Design: Cut points were developed from a previously collected data set of all level 1 trauma patients admitted January 2010 to December 2016. Objective values available on or shortly after arrival were evaluated. Once generated, we then validated these variables against (1) a prospective data set November 2017 to October 2021 of severely injured patients and (2) a multicenter, randomized trial of hemorrhagic shock patients. Analyses were conducted using STATA 17.0 (College Station, TX), generating positive predictive value (PPV), negative predictive value, sensitivity, and specificity., Results: The development data set consisted of 9,509 patients (17% mortality), with 2,137 (24%) and 680 (24%) in the two validation data sets. Several combinations of arrival vitals and labs had 100% PPV. Patients undergoing CPR in the field or on arrival (with subsequent return of spontaneous circulation) required lower fibrinolysis LY-30 (30%) than those with systolic blood pressures of ≤50 (30 to 50%), ≤70 (80 to 90%), and ≤90 mmHg (90%). Using a combination of these validated variables, the Suspension of Transfusions and Other Procedures (STOP) criteria were developed, with each element predicting 100% mortality, allowing physicians to cease further resuscitative efforts., Conclusions: The use of evidence-based STOP criteria provides cut points of futility to help guide early decisions for discontinuing aggressive treatment of severely injured patients arriving in extremis., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a well-validated method for the control of noncompressible truncal hemorrhage. In lower resource or battlefield settings, the need for arterial line setup and monitoring is problematic and potentially prohibitive. We sought to evaluate the accuracy and precision of a miniaturized portable device (Centurion COMPASS ® ) versus standard arterial pressure monitoring using standard ER-REBOA and partial REBOA (pREBOA) as a high-fidelity and space-/time-conserving alternative., Methods: A total of 40 swine underwent a four-phase validation/precision study (each phase using five ER-REBOAs and five pREBOAs). Phases I/II evaluated accuracy with full and pREBOA in uninjured animals. Phases III/IV duplicated the previous phases but in a severe hemorrhagic shock model. Carotid and femoral pressures were monitored with both intra-arterial pressure systems and the COMPASS ® device. The vascular flow was measured by aortic flow probes. Correlation and Bland-Altman analysis were performed., Results: There was a strong correlation in accuracy testing of proximal and distal COMPASS ® devices compared to standard intra-arterial pressure monitoring (r = 0.94, 0.8; p < 0.005) as well as during precision testing (r = 0.98, 0.89 p < 0.005) in the uninjured phases. Similar accuracy and reliability were demonstrated in hemorrhagic shock, with a strong correlation for the proximal and distal COMPASS ® devices (r = 0.98, 0.97; p < 0.005), as well as during precision testing (r = 0.99, 0.95; p < 0.005) in both full and pREBOA scenarios. Bland-Altman analysis showed extremely low bias between the COMPASS ® and arterial line for both proximal (bias = 1.9) and distal (bias = 0.8) pressure measurements., Conclusion: The COMPASS ® provides accurate and precise pressure measurements during standard and partial REBOA in both uninjured and shock conditions. This device may help extend and enhance capability in any low-resource/battlefield settings, or even eliminate the need for standard intra-arterial invasive pressure monitoring and external setup., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used as a temporizing procedure to control intra-abdominal or pelvic bleeding. Theoretically, occlusion of the aorta and the resulting ischemia-reperfusion of the lower extremities may increase the risk of extremity compartment syndrome (CS). To date, no study has addressed systematically the incidence and risk factors of CS following REBOA intervention. The purpose of this study was to address this knowledge gap., Methods: Adult trauma patients from the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) database (2016-2019) were included. Patients who received REBOA within 4 h of admission were compared to patients without REBOA after propensity score matching for demographics, vital signs on admission, comorbidities, injury severity of different body regions, pelvic and lower extremity fractures, vascular trauma to the lower extremities, fixation for fractures, angioembolization (AE) for pelvis, preperitoneal pelvic packing (PPP), laparotomy, and venous thromboembolism (VTE) prophylaxis. The primary outcomes were rates of lower extremity CS and fasciotomy and acute kidney injury (AKI). Secondary outcomes included mortality., Results: There were 534 patients who received REBOA matched with 1043 patients without REBOA. Overall, patients in the REBOA group had significantly higher rates of CS than no REBOA patients [5.4% vs 1.1%, p < 0.001, OR: 5.39]. The risk of CS remained significantly higher in the subgroups of patients with or without pelvic or lower extremity fractures, as well as in the subgroup of patients with associated extremity vascular injury [11.2% vs 1.5%, p < 0.001, OR: 8.12].The fasciotomy and AKI rates were significantly higher in the REBOA group (5.8% vs 1.2%, p < 0.001 and 12.9% vs 7.4%, p< 0.001 respectively)., Conclusion: REBOA use is associated with a higher risk of lower extremity CS, fasciotomy and AKI, especially in patients with associated lower extremity vascular injuries. These complications should be taken into account when considering REBOA use, and close observation for this complication should always be part of the routine monitoring., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Introduction: Agitation on arrival in trauma patients is known as a sign of impending demise. The aim of this study is to determine outcomes for trauma patients who present in an agitated state. We hypothesized that agitation in the trauma bay is an early indicator for hemorrhage in trauma patients., Methods: We performed a single-institution prospective observational study from September 2018 to December 2020 that included any trauma patient who arrived agitated, defined as a Richmond Agitation-Sedation Scale of +1 to +4. Variables collected included demographics, mechanism of injury, admission physiology, blood alcohol level, toxicity screen, and injury severity. The primary outcomes were need for massive transfusion (≥ 10 units) and need for emergent therapeutic intervention for hemorrhage control (laparotomy, preperitoneal pelvic packing, sternotomy, thoracotomy, or angioembolization)., Results: Of 4657 trauma admissions, 77 (2%) patients arrived agitated. Agitated patients were younger (40 versus 46, P = 0.03), predominantly male (94% versus 66%, P < 0.0001) sustained more penetrating trauma (31% versus 12%, P < 0.0001), had a lower systolic blood pressure (127 versus 137, P < 0.0001), and a higher Injury Severity Score (17 versus 9, P < 0.0001). On multivariable logistic regression, agitation was independently associated with massive transfusion (odds ratio: 2.63 [1.20-5.77], P = 0.02) and emergent therapeutic intervention for hemorrhage control (odds ratio: 2.60 [1.35-5.03], P = 0.005)., Conclusions: Agitation in trauma patients may serve as an early indicator of hemorrhagic shock, as agitation is independently associated with a two-fold increase in the need for massive transfusion and emergent therapeutic intervention for hemorrhage control., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: One of the advantages of partial Resuscitative Endovascular Balloon Occlusion of the Aorta (pREBOA) compared to the original model is the mitigation of reperfusion injury. The safety and efficacy of pREBOA have not been demonstrated in the setting of aeromedical evacuation. We hypothesized that the pREBOA would result in less ischemia-reperfusion injury after altitude exposure., Methods: Twenty-four swine underwent femur fracture with hemorrhage for 20 min, followed by resuscitative endovascular balloon occlusion of the aorta (REBOA) deployment to Zone 1 and were randomized to pREBOA-PRO (Prytime Medical Devices Inc) full inflation, partial inflation, or sham inflation and then an altitude exposure of ground level or 8000 ft for 15 min. The primary endpoint was to examine if the balloon functioned at altitude. Our secondary endpoint was investigating evidence of ischemia-reperfusion by hemodynamic instability, electrolyte derangements, and acidosis. Comparisons were made by ANOVA., Results: After deflation, the partially inflated group maintained a higher mean arterial pressure (MAP) compared to fully inflated group (P = 0.026). Full REBOA pigs were more tachycardic compared to sham pREBOA at ground (P < 0.001) and this was exacerbated at altitude (P < 0.001). Full REBOA pigs were more acidotic than sham and pREBOA at ground pigs (P = 0.0006 and P = 0.0002, respectively). Altitude increased the acidosis in full REBOA pigs, resulting in a greater base deficit (P < 0.0001), lactate (P < 0.0001), and IL-6 (P = 0.006)., Conclusions: PREBOA resulted in less severe ischemia-reperfusion injury at both altitude and ground, while full balloon inflation at altitude exacerbated acidosis and ischemia-reperfusion injury. Efforts should therefore be made to utilize partial balloon occlusion when employing the REBOA catheter., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Balanced transfusion is lifesaving for hemorrhagic shock. The American Red Cross critical blood shortage in 2022 threatened the immediate availability of blood. To eliminate waste, we reviewed the utility of transfusions per unit to define expected mortality at various levels of balanced transfusion., Methods: A retrospective study of 296 patients receiving massive transfusion on presentation at a level 1 trauma center was performed from January 2018 to December 2021. Units of packed red blood cells (PRBCs), fresh frozen plasma (FFP), and platelets received in the first 4 hours were recorded. Patients were excluded if they died in the emergency department, died on arrival, received <2 U PRBCs or FFP, or received PRBC/FFP >2:1. Primary outcomes were mortality and odds of survival to discharge. Subgroups were defined as transfused if receiving 2 to 9 U PRBCs, massive transfusion for 10 to 19 U PRBCs, and ultramassive transfusion for ≥20 U PRBCs., Results: A total of 207 patients were included (median age, 32 years; median Injury Severity Score, 25; 67% with penetrating mechanism). Mortality was 29% (61 of 207 patients). Odds of survival is equal to odds of mortality at 11 U PRBCs (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.50-1.79). Beyond 16 U PRBCs, odds of mortality exceed survival (OR, 0.36; 95% CI, 0.16-0.82). Survival approaches zero >36 U PRBCs (OR, 0.09; 95% CI, 0.00-0.56). Subgroup mortality rates increased with unit transfused (16% transfused vs. 36% massive transfusion, p = 0.003; 36% massive transfusion vs. 67% ultramassive transfusion, p = 0.006)., Conclusion: Mortality increases with each unit balanced transfusion. Surgeons should view efforts heroic beyond 16 U PRBCs/4 hours and near futile beyond 36 U PRBCs/4 hours. While extreme outliers can survive, consider cessation of resuscitation beyond 36 U PRBCs. This is especially true if hemostasis has not been achieved or blood supplies are limited., Level of Evidence: Prognostic and Epidemiologic; Level IV., (Copyright © 2022 American Association for the Surgery of Trauma.)

Hypoxemic arrests due to severe traumatic pulmonary injury may not respond to usual medical support. Extracorporeal life support (ECLS) can be life-saving; adequate flows are needed in this setting along with a careful choice of anticoagulation strategies to minimize bleeding. A 44 month old child, who presented with severe blunt chest trauma after being run over by a truck was resuscitated with active compressions and code medications seven times before arrival to the intensive care unit. Failure to adequately oxygenate led to an unconventional approach with cannulations of the right atrium (RA) and pulmonary artery (PA) via sternotomy. Anticoagulation regimen started after bleeding had slowed down with active transfusion of blood products and consisted of low-dose heparin and alprostadil infusions for the initial 48 hours. Heparin was adjusted per institutional guidelines thereafter. Physiologically veno-venous central approach enabled fast stabilization due to full oxygenation without recirculation. Additionally, the dual anticoagulation regimen was safe for circuit maintenance. The described method can be considered in small children with similar risks and conditions., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Abstract: Dendritic cell (DC)-mediated immune dysfunction is involved in the process of severe hemorrhagic shock that leads to sepsis. Although post-hemorrhagic shock mesenteric lymph (PHSML) induces immune organs injuries and apoptosis, whether PHSML exerts adverse effects on splenic DCs remains unknown. In this study, we established a hemorrhagic shock model (40 ± 2 mm Hg for 60 min) followed by fluid resuscitation with the shed blood and equal Ringer's solution and drained the PHSML after resuscitation. At 3 h after resuscitation, we harvested the splenic tissue to isolate DCs using anti-CD11c immunomagnetic beads and then detected the necrotic and apoptotic rates in splenocytes and splenic DCs. We also detected the levels of TNF-α, IL-10, and IL-12 in the culture supernatants and surface marker expressions of MHC-II, CD80, and CD86 of splenic DCs following LPS stimulation for 24 h. Second, we purified the DCs from splenocytes of normal mice to investigate the effects of PHSML treatment on cytokine production and surface marker expression following LPS stimulation. The results showed that PHSML drainage attenuated LPS-induced cell death of splenocytes and DCs. Meanwhile, PHSML drainage enhanced the DC percentage in splenocytes and increased the TNF-α and IL-12 production by DCs and the expressions of CD80, CD86, and MHCII of DCs treated by LPS. Furthermore, PHSML treatment reduced the productions of TNF-α, IL-10, and IL-12 and the expressions of CD80 and CD86 in normal DCs after treatment with LPS. In summary, the current investigation demonstrated that PHSML inhibited the cytokine production and surface marker expressions of DCs stimulated by LPS, suggesting that PHSML plays an important role in hemorrhagic shock-induced immunosuppression through the impairment of DC function and maturation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Background: Early recognition and intervention of hemorrhage are associated with decreased morbidity in children. Triage models have been developed to aid in the recognition of hemorrhagic shock after injury but require complete data and have limited accuracy. To address these limitations, we developed a Bayesian belief network, a machine learning model that represents the joint probability distribution for a set of observed or unobserved independent variables, to predict blood transfusion after injury in children and adolescents., Methods: We abstracted patient, injury, and resuscitation characteristics of injured children and adolescents (age 1 to 18 years) from the 2017 to 2019 Trauma Quality Improvement Project database. We trained a Bayesian belief network to predict blood transfusion within 4 hours after arrival to the hospital following injury using data from 2017 and recalibrated the model using data from 2018. We validated our model on a subset of patients from the 2019 Trauma Quality Improvement Project. We evaluated model performance using the area under the receiver operating characteristic curve and calibration curves and compared performance with pediatric age-adjusted shock index (SIPA) and reverse shock index with Glasgow Coma Scale (rSIG) using sensitivity, specificity, accuracy, and Matthew's correlation coefficient (MCC)., Results: The final model included 14 predictor variables and had excellent discrimination and calibration. The model achieved an area under the receiver operating characteristic curve of 0.92 using emergency department data. When used as a binary predictor at an optimal threshold probability, the model had similar sensitivity, specificity, accuracy, and MCC compared with SIPA when only age, systolic blood pressure, and heart rate were observed. With the addition of the Glasgow Coma Scale score, the model has a higher accuracy and MCC than SIPA and rSIG., Conclusion: A Bayesian belief network predicted blood transfusion after injury in children and adolescents better than SIPA and rSIG. This probabilistic model may allow clinicians to stratify hemorrhagic control interventions based upon risk., Level of Evidence: Prognostic and Epidemiologic; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Aortic occlusion (AO) is a lifesaving therapy for the treatment of severe traumatic hemorrhagic shock; however, there remains controversy whether AO should be accomplished via resuscitative thoracotomy (RT) or via endovascular balloon occlusion of the aorta (REBOA) in zone 1., Objective: To compare outcomes of AO via RT vs REBOA zone 1., Design, Setting, and Participants: This was a comparative effectiveness research study using a multicenter registry of postinjury AO from October 2013 to September 2021. AO via REBOA zone 1 (above celiac artery) was compared with RT performed in the emergency department of facilities experienced in both procedures and documented in the prospective multicenter Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry. Propensity score matching (PSM) with exact institution matching was used, in addition to subgroup multivariate analysis to control for confounders. The study setting included the ED, where AO via RT or REBOA was performed, and participants were adult trauma patients 16 years or older., Exposures: AO via REBOA zone 1 vs RT., Main Outcomes and Measures: The primary outcome was survival. Secondary outcomes were ventilation-free days (VFDs), intensive care unit (ICU)-free days, discharge Glasgow Coma Scale score, and Glasgow Outcome Score (GOS)., Results: A total of 991 patients (median [IQR] age, 32 [25-48] years; 808 male individuals [81.9%]) with a median (IQR) Injury Severity Score of 29 (18-50) were included. Of the total participants, 306 (30.9%) had AO via REBOA zone 1, and 685 (69.1%) had AO via RT. PSM selected 112 comparable patients (56 pairs). REBOA zone 1 was associated with a statistically significant lower mortality compared with RT (78.6% [44] vs 92.9% [52]; P = .03). There were no significant differences in VFD greater than 0 (REBOA, 18.5% [10] vs RT, 7.1% [4]; P = .07), ICU-free days greater than 0 (REBOA, 18.2% [10] vs RT, 7.1% [4]; P = .08), or discharge GOS of 5 or more (REBOA, 7.5% [4] vs RT, 3.6% [2]; P = .38). Multivariate analysis confirmed the survival benefit of REBOA zone 1 after adjustment for significant confounders (relative risk [RR], 1.25; 95% CI, 1.15-1.36). In all subgroup analyses (cardiopulmonary resuscitation on arrival, traumatic brain injury, chest injury, pelvic injury, blunt/penetrating mechanism, systolic blood pressure ≤60 mm Hg on AO initiation), REBOA zone 1 offered an either similar or superior survival., Conclusions and Relevance: Results of this comparative effectiveness research suggest that REBOA zone 1 provided better or similar survival than RT for patients requiring AO postinjury. These findings provide the ethically necessary equipoise between these therapeutic approaches to allow the planning of a randomized controlled trial to establish the safety and effectiveness of REBOA zone 1 for AO in trauma resuscitation.

Background: Severe pelvic fracture is the most common indication for resuscitative endovascular balloon occlusion of the aorta (REBOA). This matched cohort study investigated outcomes with or without REBOA use in isolated severe pelvic fractures., Methods: Trauma Quality Improvement Program database study, included patients with isolated severe pelvic fracture (AIS≥3), excluded associated injuries with AIS >3 for any region other than lower extremity. REBOA patients were propensity score matched to similar patients without REBOA. Outcomes were mortality and complications., Results: 93 REBOA patients were matched with 279 without. REBOA patients had higher rates of in-hospital mortality (32.3% vs 19%, p = 0.008), higher rates of venous thromboembolism (14% vs 6.5%, p = 0.023) and DVT (11.8% vs 5.4%, p = 0.035). In multivariate analysis, REBOA use was independently associated with increased mortality and venous thromboembolism., Conclusions: REBOA in severe pelvic fractures is associated with higher rates of mortality, venous thromboembolism., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Haemorrhagic shock remains a leading preventable cause of death amongst trauma patients. Failure to identify retroperitoneal haemorrhage (RPH) can lead to irreversible haemorrhagic shock. The arteries of the middle retroperitoneal region (i.e., the 1st to 4th lumbar arteries) are complicit in haemorrhage into the retroperitoneal space. However, predictive injury patterns and subsequent management implications of haemorrhage secondary to bleeding of these arteries is lacking., Materials and Methods: We performed a retrospective cohort study of patients diagnosed with retroperitoneal haemorrhage who presented to our Level-1 Trauma Centre (2009-2019). We described the associated injuries, management and outcomes relating to haemorrhage of lumbar arteries (L1-4) from this cohort to assess risk and management priorities in non-cavitary haemorrhage compared to RPH due to other causes., Results: Haemorrhage of the lumbar arteries (LA) is associated with a higher proportion of lumbar transverse process (TP) fractures. Bleeding from branches of these vessels is associated with lower systolic blood pressure, increased incidence of massive transfusion, higher shock index, and a higher Injury Severity Score (ISS). A higher proportion of patients in the LA group underwent angioembolisation when compared to other causes of RPH., Conclusion: This study highlights the injury patterns, particularly TP fractures, in the prediction, early detection and management of haemorrhage from the lumbar arteries (L1-4). Compared to other causes of RPH, bleeding of the LA responds to early, aggressive haemorrhage control through angioembolisation. These injuries are likely best treated in Level-1 or Level-2 trauma facilities that are equipped with angioembolisation facilities or hybrid theatres to facilitate early identification and management of thoracolumbar bleeds., Competing Interests: Declaration of Competing Interest We declare no financial or personal interest or belief that could affect the objectivity and validity of this research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Prehospital transfusion capabilities vary widely in the United States. Here we describe a case of prehospital resuscitation using warmed, whole blood in a patient with penetrating torso trauma and associated hemorrhagic shock., Case Report: A 68-year-old man sustained a single gunshot wound to the left chest and was found to have a shock index of 1.5 at the time of emergency medical services (EMS) arrival. Rapid peripheral intravenous and central venous access enabled the infusion of warmed low-titer O-positive whole blood. The EMS crew intentionally resuscitated the patient before managing the airway by means of rapid sequence intubation. An air medical services helicopter crew assumed patient care from the ground EMS crew and continued the warmed, whole blood transfusion during the flight to a regional Level I trauma center. The patient went directly to the operating room from the helipad, underwent definitive operative management, and was ultimately discharged home on hospital day nine., Conclusion: Early recognition of hemorrhagic shock, implementation of prehospital transfusion protocols that emphasize transfusion of warmed blood without interruption, and an organized, regional approach to trauma care are critical for improving patient survival.

Abstract: The original guidelines of cardiopulmonary resuscitation focused on the establishment of an airway and rescue breathing before restoration of circulation through cardiopulmonary resuscitation. As a result, the airway-breathing-circulation approach became the central guiding principle of resuscitation. Despite new guidelines by the American Heart Association for a circulation-first approach, Advanced Trauma Life Support guidelines continue to advocate for the airway-breathing-circulation sequence. Although definitive airway management is often necessary for severely injured patients, endotracheal intubation (ETI) before resuscitation in patients with hemorrhagic shock may worsen hypotension and precipitate cardiac arrest. In severely injured patients, a paradigm shift should be considered, which prioritizes restoration of circulation before ETI and positive pressure ventilation while maintaining a focus on basic airway assessment and noninvasive airway interventions. For this patient population, the most reasonable current strategy may be to target a simultaneous resuscitation approach, with immediate efforts to control hemorrhage and provide basic airway interventions while prioritizing volume resuscitation with blood products and deferring ETI until adequate systemic perfusion has been attained. We believe that a circulation-first sequence will improve both survival and neurologic outcomes for a traumatically injured patient and will continue to advocate this approach, as additional clinical evidence is generated to inform how to best tailor circulation-first resuscitation for varied injury patterns and patient populations., (Copyright © 2022 by the Shock Society.)

Abstract: Increasing rates of penetrating trauma in the United States makes rapid identification of hemorrhagic shock, coagulopathy, and early initiation of balanced resuscitation in injured children of critical importance. Hemorrhagic shock begins early after injury and can be challenging to identify in children, as hypotension is a late sign that a child is on the verge of circulatory collapse and should be aggressively resuscitated. Recent data support shifting away from crystalloid and toward early resuscitation with blood products because of worse coagulopathy and clinical outcomes in injured patients resuscitated with crystalloid. Multicenter studies have found improved survival in injured children who receive balanced resuscitation with higher fresh frozen plasma: red blood cell ratios. Whole blood is an efficient way to achieve balanced resuscitation in critically injured children with limited intravenous access and decreased exposure to multiple donors. Administration of cold-stored, low-titer O-negative whole blood (LTOWB) appears to be safe in adults and children and may be associated with improved survival in children with life-threatening hemorrhage. Many pediatric centers use RhD-negative LTOWB for all female children because of the risk of hemolytic disease of the fetus and newborn (0-6%); however. there is a scarcity of LTOWB compared with the demand. Low risks of hemolytic disease of the fetus and newborn affecting a future pregnancy must be weighed against high mortality rates in delayed blood product administration in children in hemorrhagic shock. Survey studies involving key stakeholder's opinions on pediatric blood transfusion practices are underway. Existing pediatric-specific literature on trauma resuscitation is often limited and underpowered; multicenter prospective studies are urgently needed to define optimal resuscitation products and practices in injured children in an era of increasing penetrating trauma., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is a potential method to mitigate the ischemia observed in full REBOA (fREBOA). However, the effect of pREBOA on cerebral perfusion in the setting of raised intracranial pressure (rICP) is unknown. The aim was to evaluate the effects of no REBOA (nREBOA) vs pREBOA vs fREBOA on cerebral perfusion in a swine model of rICP and hemorrhagic shock., Study Design: Anesthetized swine (n = 18) underwent instrumentation. Controlled hemorrhage was performed over 30 minutes. rICP was achieved using an intracranial Fogarty catheter inflated to achieve an ICP of 20 mmHg. Animals underwent intervention for 30 minutes, followed by resuscitation. The primary outcome was cerebral perfusion measured by ICP (millimeters of mercury), cerebral perfusion pressure (CPP; millimeters of mercury), and cerebral blood flow (CBF; milliliters per minute per 100 g) derived from CT perfusion. The secondary outcomes included hemodynamics and lactate (millimoles per liter)., Results: The peak ICP of pREBOA animals (22.7 ± 2.5) was significantly lower than nREBOA and fREBOA. pREBOA CPP was significantly higher compared with nREBOA and fREBOA during resuscitation. The pREBOA CBF was greater during intervention and resuscitation compared with nREBOA (p < 0.001). Systolic blood pressure was similar between pREBOA and fREBOA, and coronary perfusion was significantly greater in pREBOA. fREBOA had significantly higher lactate during the intervention (9.3 ± 1.3) and resuscitation (8.9 ± 3.5) compared with nREBOA and pREBOA., Conclusion: pREBOA produced greater cerebral perfusion, as demonstrated by more favorable CPP, CBF, and ICP values. fREBOA was associated with metabolic derangement and diminished pressure during resuscitation. pREBOA is superior to fREBOA in a swine model and should be considered over fREBOA for aortic occlusion., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock., Methods: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were informed by a systematic review of topics in this area and a discussion of these areas in the consensus conference. Research priorities were synthesized along themes and prioritized by anonymous voting., Results: Eleven research priorities that warrant additional investigation were identified by the consensus committee. Areas of proposed study included well-designed clinical trials and evaluations, including increasing the speed and accuracy of identifying and treating hemorrhagic shock, defining the role of whole blood and tranexamic acid use, and assessment of the utility and appropriate use of viscoelastic techniques during early resuscitation. The committee recommended the need to standardize essential definitions, data elements, and data collection to facilitate research in this area., Conclusion: Research gaps remain in many areas related to the care of hemorrhagic shock after pediatric injury. Addressing these gaps is needed to develop improved evidence-based recommendations for the care of pediatric trauma patients in hemorrhagic shock., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Strategies to improve outcomes among children and adolescents in hemorrhagic shock have primarily focused on component resuscitation, pharmaceutical coagulation adjuncts, and hemorrhage control techniques. Many of these strategies have been associated with better outcomes in children, but the barriers to their use and the impact of timely use on morbidity and mortality have received little attention. Because transfusion is uncommon in injured children, few studies have identified and described barriers to the processes of using these interventions in bleeding patients, processes that move from the decision to transfuse, to obtaining the necessary blood products and adjuncts, and to delivering them to the patient. In this review, we identify and describe the steps needed to ensure timely blood transfusion and propose practices to minimize barriers in this process. Given the potential impact of time on hemorrhage associated outcomes, ensuring timely intervention may have a similar or greater impact than the interventions themselves., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early damage control resuscitation and massive transfusion (MT) protocol activations improve outcomes in trauma patients with hemorrhagic shock, where scores to guide MT prediction are used including: the Assessment of Blood Consumption (ABC), Shock Index (SI), and Revised Assessment of Bleeding and Transfusion (RABT) scores. Our aim was to validate the RABT score in patients from two level I trauma centers in Canada., Methods: A retrospective review of adult patients meeting trauma team activation criteria receiving >1 unit of red blood cells (RBCs) within 24 h of admission, from 2015 to 2020, was conducted. A RABT score ≥ 2, ABC score ≥ 2, and Shock Index (SI) ≥ 1 was used to predict MT using both research (≥10 RBCs in 24 h) and clinical (≥3 RBCs in 3 h) definitions. Scores were assessed and compared using sensitivity, specificity, and the area under the receiver operating characteristic (AUROC)., Results: We analyzed 514 patients with a mean age of 44.4 (19.2) years and a median injury severity score of 29 [18-38]. For both MT definitions, the RABT score trended towards higher sensitivity and lower specificity compared to ABC score and SI. For both research and clinical definitions of MT, the AUROC for the RABT score was not significantly higher (Research - RABT: 0.673 [0.610-0.735], ABC: 0.642 [0.551-0.734], SI 0.691 [0.625-0.757]; Clinical - RABT: 0.653 [0.608-0.698], ABC: 0.646 [0.600-0.691], SI 0.610 [0.559-0.660])., Conclusion: The RABT score is a valid tool for predicting the need for MTPs, performing similarly with a trend towards higher sensitivity when compared to the ABC score and SI., Competing Interests: Declaration of Competing Interest No authors have any conflicts of interest, (Copyright © 2022. Published by Elsevier Ltd.)

Background: Gastroesophageal resuscitative occlusion of the aorta (GROA) has been shown effective in creating zone II aortic occlusion capable of temporarily improving survival in animal models of lethal noncompressible torso hemorrhage. In this study, tandem application of GROA transitioning to resuscitative endovascular balloon occlusion of the aorta (REBOA) is explored to demonstrate feasibility as a potential point-of-injury bridge to more advanced care, using a swine model of lethal abdominal hemorrhage., Methods: Swine (n = 19) were anesthetized, instrumented, and subjected to a combination of controlled and uncontrolled hemorrhage from a grade-V liver laceration. Animals were designated as intervention (n = 9; GROA to REBOA) or control (n = 10), for 60 minutes. Following intervention, devices were deactivated, and animals received blood and crystalloid resuscitation. Animals were monitored for 4 hours., Results: Injury resulted in onset of class IV shock in all animals with a mean arterial pressure (SD) of 24.5 (4.11) mm Hg at the start of intervention. Nine of 10 controls died during the intervention period with a median (interquartile) survival time of 8.5 (9.25) minutes. All animals receiving the intervention survived both the 60-minute intervention period demonstrating a significant survival improvement ( p = 0.0007). Transition from GROA to REBOA was successful in all animals with a transition time ranging from 30 to 90 seconds. Mean arterial pressure significantly improved in animals receiving GROA to REBOA for the duration of intervention, regardless of the method of aortic occlusion, with a range of 70.9 (16.04) mm Hg to 101.1 (15.3) mm Hg. Additional hemodynamics, metrics of shock, and oxygenation remained stable during intervention., Conclusion: Less invasive technologies such as GROA may present an opportunity to control noncompressible torso hemorrhage more rapidly, with a subsequent transition to more advanced care such as REBOA., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Myocardial dysfunction played a vital role in organ damage after sepsis. Fluid resuscitation was the essential treatment in which Lactate Ringer's solution (LR) was commonly used. Since LR easily led to hyperlactatemia, its resuscitation effect was limited. Malate Ringer's solution (MR) was a new resuscitation crystal liquid. Whether MR had a protective effect on myocardial injury in sepsis and the relevant mechanism need to be studied., Methods: The cecal ligation and puncture (CLP) inducing septic model and lipopolysaccharide (LPS) stimulating cardiomyocytes were used, and the cardiac function, the morphology and function of mitochondria were observed. The protective mechanism of MR on myocardial injury was explored by proteomics. Then the effects of TPP@PAMAM-MR, which consisted of the mitochondria- targeting polymer embodied malic acid, was further observed., Results: Compared with LR, MR resuscitation significantly prolonged survival time, improved the cardiac function, alleviated the damages of liver, kidney and lung following sepsis in rats. The proteomics of myocardial tissue showed that differently expressed proteins between MR and LR infusion involved oxidative phosphorylation, apoptosis. Further study found that MR decreased ROS, improved the mitochondrial morphology and function, and ultimately enhanced mitochondrial respiration and promoted ATP production. Moreover, MR infusion decreased the expression of apoptosis-related proteins and increased the expression of anti-apoptotic proteins. TPP@PAMAM@MA was a polymer formed by wrapping L-malic acid with poly amido amine (PAMAM) modified triphenylphosphine material. TPP@PAMAM-MR (TPP-MR), which was synthesized by replacing the L-malic acid of MR with TPP@PAMAM@MA, was more efficient in targeting myocardial mitochondria and was superior to MR in protecting the sepsis-inducing myocardial injury., Conclusion: MR was suitable for protecting myocardial injury after sepsis. The mechanism was related to MR improving the function and morphology of cardiomyocyte mitochondria and inhibiting cardiomyocyte apoptosis. The protective effect of TPP-MR was superior to MR., (© 2022. The Author(s).)

Background: Early balanced transfusion is associated with improved outcome in haemorrhagic shock patients. This study describes the implementation and evaluates the safety of a whole blood transfusion program in a civilian helicopter emergency medical service (HEMS)., Methods: This prospective observational study was performed over a 5-year period at HEMS-Bergen, Norway. Patients in haemorrhagic shock receiving out of hospital transfusion of low-titre Group O whole blood (LTOWB) or other blood components were included. Two LTOWB units were produced weekly and rotated to the HEMS for forward storage. The primary endpoints were the number of patients transfused, mechanisms of injury/illness, adverse events and survival rates. Informed consent covered patient pathway from time of emergency interventions to last endpoint and subsequent data handling/storage., Results: The HEMS responded to 5124 patients. Seventy-two (1.4%) patients received transfusions. Twenty patients (28%) were excluded due to lack of consent (16) or not meeting the inclusion criteria (4). Of the 52 (100%) patients, 48 (92%) received LTOWB, nine (17%) received packed red blood cells (PRBC), and nine (17%) received freeze-dried plasma. Of the forty-six (88%) patients admitted alive to hospital, 35 (76%) received additional blood transfusions during the first 24 h. Categories were blunt trauma 30 (58%), penetrating trauma 7 (13%), and nontrauma 15 (29%). The majority (79%) were male, with a median age of 49 (IQR 27-70) years. No transfusion reactions, serious complications or logistical challenges were reported. Overall, 36 (69%) patients survived 24 h, and 28 (54%) survived 30 days., Conclusions: Implementing a whole blood transfusion program in civilian HEMS is feasible and safe and the logistics around out of hospital whole blood transfusions are manageable. Trial registration The study is registered in the ClinicalTrials.gov registry (NCT02784951)., (© 2022. The Author(s).)

Background: Patients suffering from severe trauma experience substantial immunological stress. Lung injury is a known risk factor for the development of posttraumatic complications, but information on the long-term course of the pulmonary inflammatory response and treatment with mild hypothermia are scarce., Aim: To investigate the pulmonary inflammatory response to multiple trauma and hemorrhagic shock in a porcine model of combined trauma and to assess the immunomodulatory properties of mild hypothermia., Methods: Following induction of trauma (blunt chest trauma, liver laceration, tibia fracture), two degrees of hemorrhagic shock (45 and 50%) over 90 (n = 30) and 120 min. (n = 20) were induced. Animals were randomized to hypothermia (33°C) or normothermia (38°C). We evaluated bronchoalveolar lavage (BAL) fluid and tissue levels of cytokines and investigated changes in microRNA- and gene-expression as well as tissue apoptosis., Results: We observed a significant induction of Interleukin (IL) 1β, IL-6, IL-8, and Cyclooxygenase-2 mRNA in lung tissue. Likewise, an increased IL-6 protein concentration could be detected in BAL-fluid, with a slight decrease of IL-6 protein in animals treated with hypothermia. Lower IL-10 protein levels in normothermia and higher IL-10 protein concentrations in hypothermia accompanied this trend. Tissue apoptosis increased after trauma. However, intervention with hypothermia did not result in a meaningful reduction of pro-inflammatory biomarkers or tissue apoptosis., Conclusion: We observed signs of a time-dependent pulmonary inflammation and apoptosis at the site of severe trauma, and to a lower extent in the trauma-distant lung. Intervention with mild hypothermia had no considerable effect during 48 hours following trauma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Oestreich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose of Review: Transfusion of blood products is lifesaving in the trauma ICU. Intensivists must be familiar with contemporary literature to develop the optimal transfusion strategy for each patient., Recent Findings: A balanced ratio of red-blood cells to plasma and platelets is associated with improved mortality and has therefore become the standard of care for resuscitation. There is a dose-dependent relationship between units of product transfused and infections. Liquid and freeze-dried plasma are alternatives to fresh frozen plasma that can be administered immediately and may improve coagulation parameters more rapidly, though higher quality research is needed. Trauma induced coagulopathy can occur despite a balanced transfusion, and administration of prothrombin complex concentrate and cryoprecipitate may have a role in preventing this. In addition to balanced ratios, viscoelastic guidance is being increasingly utilized to individualize component transfusion. Alternatively, whole blood can be used, which has become the standard in military practice and is gaining popularity at civilian centers., Summary: Hemorrhagic shock is the leading cause of death in trauma. Improved resuscitation strategy has been one of the most important contemporary advancements in trauma care and continues to be a key area of clinical research., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Hemorrhage is the leading cause of preventable death, with a majority of mortalities in the prehospital setting. Current hemorrhage resuscitation guidelines cannot predict the critical point of intervention to activate massive transfusion (MT) and prevent cardiovascular decompensation. We hypothesized that cerebral regional tissue oxygenation (CrSO 2 ) would indicate MT need in nonhuman primate models of hemorrhagic shock., Methods: Nineteen anesthetized male rhesus macaques underwent hemorrhage via a volume-targeted (VT) or pressure-targeted (PT) method. VT animals were monitored for 30 min following 30% blood volume hemorrhage. PT animals were hemorrhaged to mean arterial pressure (MAP) of 20 mmHg and maintained for at least 60 min until decompensation. Statistics for MAP, heart rate (HR), end tidal carbon dioxide (EtCO 2 ), and CrSO 2 were analyzed via one- or two-way repeated-measures analysis of variance, Pearson's R, and receiver-operator curve. A P < 0.05 is considered significant., Results: Following initial hemorrhage (S0), there were no significant differences between groups. After cessation of hemorrhage in the VT group, MAP and EtCO 2 returned to baseline while CrSO 2 plateaued. The PT group maintained model-defined low MAP, suppressing EtCO 2 , and significantly decreased CrSO 2 compared to the VT group by S25. Linear regression of CrSO 2 versus shed blood volume demonstrated R 2  = 0.7539. CrSO 2 of 47% was able to detect >40% blood loss with an area under the curve of 0.9834 at 92.3% (66.7%-99.6%) sensitivity and 95.5% (84.9%-99.2%) specificity., Conclusions: Regardless of hemorrhage modality and compensatory response, CrSO 2 correlated strongly with shed blood volume. Analysis demonstrated that CrSO 2 values below 49% indicate Advanced Trauma Life Support class IV shock (blood loss>40%). CrSO 2 at the point of care may help indicate MT need earlier and more accurately than traditional markers., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Traumatic hemorrhagic shock (THS) is a complex, dynamic process and, no consensual definition of THS is available. This study aims (1) to explore existing definitions of traumatic hemorrhagic shock (THS), (2) to identify essential components of these definitions and (3) to illustrate in a pragmatic way the consequences of applying five of these definitions to a trauma registry., Methods: We conducted (1) a scoping review to identify the definitions used for traumatic hemorrhagic shock (THS); (2) an international experts survey to rank by relevance a selection of components extracted from these definitions and (3) a registry-based analysis where several candidate definitions were tested in a large trauma registry to evaluate how the use of different definitions affected baseline characteristics, resources use and patient outcome., Results: Sixty-eight studies were included revealing 52 distinct definitions. The most frequently used was "a systolic blood pressure (SBP) less than or equal to 70 mmHg or between 71 and 90 mmHg if the heart rate is greater than or equal to 108 beats per min". The expert panel identified base excess, blood lactate concentration, SBP and shock index as the most relevant physiological components to define THS. Five definitions of THS were tested and highlighted significant differences across groups on important outcomes such as the proportion of massive transfusion, the need for surgery, in-hospital length of stay or in-hospital mortality., Conclusions: This study demonstrates a large heterogeneity in the definitions of THS suggesting a need for standardization. Five candidate definitions were identified in a three-step process to illustrate how each shapes study cohort composition and impacts outcome. The results inform research stakeholders in the choice of a consensual definition., (© 2022. The Author(s).)

Introduction: Limitations such as time-dependent distal ischemia have slowed the adoption of resuscitative endovascular balloon occlusion of the aorta (REBOA) for noncompressible hemorrhage. Next-generation REBOA technologies may allow for controlled partial flow, known as targeted regional optimization, to reduce distal ischemia. We aimed to characterize the efficacy of one such catheter in a porcine model of lethal hemorrhagic shock., Methods: Noncompressible hemorrhage from an iliac injury was induced in anesthetized swine (Sus scrofa) (70-90 kg), targeting 30% total blood volume. Animals were then randomized to partial aortic occlusion (PO) with targeted distal mean arterial pressure (MAP) of 35-40 mm of mercury (mm Hg) and complete aortic occlusion (CO) (n = 8 per group) for 90 min. All groups were then resuscitated during a two-h critical care (CC) phase, with flow rate and MAP recorded continuously at the distal infrarenal aorta and proximal carotid artery, and analyzed with two-way repeated measures analysis of variance with S-N-K post-hoc test., Results: During aortic occlusion, MAP distal to the balloon was consistently maintained at 35.8 ± 0.3 mm Hg in the PO group compared to 27.1 ± 0.3 mm Hg in the CO group (P < 0.05), which also corresponded to higher flow rates (202.9 ± 4.8 mL/min PO versus 25.9 ± 0.8 mL/min CO; P < 0.05). MAP proximal to the balloon was significantly higher with CO versus PO (109.2 ± 2.3 mm Hg versus 85.2 ± 2.3 mm Hg; P < 0.05). During the CC phase, distal aortic flow and MAP were not significantly different between groups. However, creatinine returned to baseline levels by the end of the study in the PO group, but not the CO group. One animal died in the CO group, whereas none died in the PO group., Conclusions: This is the first examination of the next-generation pREBOA-PRO in a porcine model of lethal hemorrhagic shock. We show technical feasibility of this technique to precisely achieve targeted regional optimization without device failure or complication. The ability to titrate balloon inflation and thus distal flow/pressure may extend the therapeutic window of REBOA by mitigating distal ischemia., (Copyright © 2022. Published by Elsevier Inc.)

Objective: This guideline aims to provide evidence for prevention, recognition, and treatment of postpartum hemorrhage including severe hemorrhage leading to hemorrhagic shock., Target Population: All pregnant patients., Benefits, Harms, and Costs: Appropriate recognition and treatment of postpartum hemorrhage can prevent serious morbidity while reducing costs to the health care system by minimizing more costly interventions and length of hospital stays., Evidence: Medical literature, PubMed, ClinicalTrials.gov, the Cochrane Database, and grey literature were searched for articles, published between 2012 and 2021, on postpartum hemorrhage, uterotonics, obstetrical hemorrhage, and massive hemorrhage protocols., Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations)., Intended Audience: All members of the health care team who care for labouring or postpartum women, including, but not restricted to, nurses, midwives, family physicians, obstetricians, and anesthesiologists., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Our trauma performance improvement initiative recognized missed treatment opportunities for patients undergoing massive transfusion. To improve patient care, we developed a novel cognitive aid in the form of a poster entitled "TACTICS for Hemorrhagic Shock." We hypothesized that this reference and corresponding course would improve the performance of trauma leaders caring for simulated patients requiring massive transfusion., Methods: First, residents and physician assistants participated in a one-on-one, socially distanced, screen-based virtual patient simulation. Next, they watched a short presentation introducing the TACTICS visual aid. They then underwent a similar second virtual simulation during which they had access to the reference. In both simulations, the participants were assessed using a scoring system developed to measure their ability to provide appropriate predetermined interventions while leading a trauma resuscitation (score range, 0-100%). Preintervention and postintervention scores were compared using a one-group pre-post within-subject design. Participants' feedback was obtained anonymously., Results: Thirty-two participants (21 residents and 11 physician assistants) completed the course. The median score for the first simulation without the use of the visual aid was 43.8% (interquartile range, 33.3.8-61.5%). Commonly missed treatments included giving tranexamic acid (success rate, 37.5%), treating hypothermia (31.3%), and reversing known anticoagulation (28.1%). All participants' performance improved using the visual aid, and the median score of the second simulation was 89.6% (interquartile range, 79.2-94.8%; p < 0.001). Ninety-two percent of survey respondents "strongly agreed" that the TACTICS visual aid would be a helpful reference during real-life trauma resuscitations., Conclusion: The TACTICS visual aid is a useful tool for improving the performance of the trauma leader and is now displayed in our emergency department resuscitation rooms. This performance improvement course, the associated simulations, and visual aid are easily and virtually accessible to interested trauma programs., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2022 American Association for the Surgery of Trauma.)

For the past thirty years, hemoglobin-based oxygen carriers (HBOCs) have been under development as a red blood cell substitute. Side-effects such as vasoconstriction, oxidative injury, and cardiac toxicity have prevented clinical approval of HBOCs. Recently, high molecular weight (MW) polymerized human hemoglobin (PolyhHb) has shown positive results in rats. Studies have demonstrated that high MW PolyhHb increased O 2 delivery, with minimal effects on blood pressure, without vasoconstriction, and devoid of toxicity. In this study, we used guinea pigs to evaluate the efficacy and safety of high MW PolyhHb, since like humans guinea pigs cannot produce endogenous ascorbic acid, which limits the capacity of both species to deal with oxidative stress. Hence, this study evaluated the efficacy and safety of resuscitation from severe hemorrhagic shock with high MW PolyhHb, fresh blood, and blood stored for 2 weeks. Animals were randomly assigned to each experimental group, and hemorrhage was induced by the withdrawal of 40% of the blood volume (BV, estimated as 7.5% of body weight) from the carotid artery catheter. Hypovolemic shock was maintained for 50 min. Resuscitation was implemented by infusing 25% of the animal's BV with the different treatments. Hemodynamics, blood gases, total hemoglobin, and lactate were not different before hemorrhage and during shock between groups. The hematocrit was lower for the PolyhHb group compared to the fresh and stored blood groups after resuscitation. Resuscitation with stored blood had lower blood pressure compared to fresh blood at 2 h. There was no difference in mean arterial pressure between groups at 24 h. Resuscitation with PolyhHb was not different from fresh blood for most parameters. Resuscitation with PolyhHb did not show any remarkable change in liver injury, inflammation, or cardiac damage. Resuscitation with stored blood showed changes in liver function and inflammation, but no kidney injury or systemic inflammation. Resuscitation with stored blood after 24 h displayed sympathetic hyper-activation and signs of cardiac injury. These results suggest that PolyhHb is an effective resuscitation alternative to blood. The decreased toxicities in terms of cardiac injury markers, vital organ function, and inflammation following PolyhHb resuscitation in guinea pigs indicate a favorable safety profile. These results are promising and support future studies with this new generation of PolyhHb as alternative to blood when blood is unavailable., (© 2022. The Author(s).)

Background and Objectives : Transfusion of red cell concentrates is a key component of medical therapy. To investigate the complex transfusion-associated biochemical and physiological processes as well as potential risks for human recipients, animal models are of particular importance. This scoping review summarizes existing large animal transfusion models for their ability to model the physiology associated with the storage of erythrocyte concentrates. Materials and Methods : The electronic databases PubMed, EMBASE, and Web of Science were systematically searched for original studies providing information on the intravenous application of erythrocyte concentrates in porcine, ovine, and canine animal models. Results : A total of 36 studies were included in the analysis. The majority of porcine studies evaluated hemorrhagic shock conditions. Pig models showed high physiological similarities with regard to red cell physiology during early storage. Ovine and canine studies were found to model typical aspects of human red cell storage at 42 days. Only four studies provided data on 24 h in vivo survival of red cells. Conclusions : While ovine and canine models can mimic typical human erythrocyte storage for up to 42 days, porcine models stand out for reliably simulating double-hit pathologies such as hemorrhagic shock. Large animal models remain an important area of translational research since they have an impact on testing new pharmacological or biophysical interventions to attenuate storage-related adverse effects and allow, in a controlled environment, to study background and interventions in dynamic and severe disease conditions.

Background: Isotonic crystalloids are the preferred solution for the initial clinical management of patients with multiple trauma, among which lactated Ringer's solution and normal saline are the most widely used, but both have clinical limitations. Bicarbonated Ringer's solution (BRS), which provides physiological levels of bicarbonate ions and electrolyte ions, can be used to supplement missing extracellular fluid and correct metabolic acidosis., Methods: A prospective, randomized controlled study enrolled 63 patients with traumatic hepatic rupture and hemorrhagic shock. They were randomly assigned to the Bicarbonated group (n = 33) or the Control group (n = 30), which received restrictive fluid resuscitation with sodium bicarbonate Ringer's solution or sodium lactate Ringer's solution, respectively. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, arterial blood lactic acid and potential of hydrogen (pH) were measured prior to, 1, 3, 24, and 72 hours following resuscitation. The primary outcomes were patient survival, shock-related complications, and comparison of the inflammatory factors., Results: The incidence of complications in the Bicarbonated group was significantly lower than in the Control group (15.15% vs 40.0%; P < .05). The intensive care unit length of stay and mechanical ventilation time in the Bicarbonated group were significantly shorter than in the Control group (all P < .01). The levels of IL-6 and TNF-α in the Bicarbonated group were significantly lower 1 hour following resuscitation than prior to resuscitation (P < .01), whereas these levels in the Control group were increased following 1h of resuscitation as compared with before resuscitation (P < .01). Following resuscitation, the levels of IL-6, TNF-α and lactate in the Bicarbonated group were significantly lower than in the Control group (P < .01). Moreover, in the Bicarbonated group, the lactic acid level decreased and the pH value increased significantly following resuscitation, whereas there was no difference in lactic acid levels and pH value between pre- and 1 hour post-resuscitation in the Control group (P > .05)., Conclusion: The shock-related complications were dramatically reduced from using BRS in these patients. Additionally, the BRS was found to better inhibit the expression of inflammatory factors in their peripheral blood and could correct acidosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Resuscitative endovascular balloon occlusion of the aorta (REBOA) increases proximal blood pressure while inducing distal ischemia of visceral organs. The evaluation of distal ischemia severity during REBOA is a prerequisite for safe resuscitation of haemorrhagic shock patients with REBOA. We evaluated changes in blood flow and organ perfusion due to the degree of occlusion using dynamic 4D-computed tomography (CT). We compared the results with those of a previous study on euvolemic status. Delayed enhancement of the inferior vena cava (IVC) without retrograde flow was observed in the 4D-volume rendering images in the high-degree occlusion. The time-density curve (TDC) of the liver parenchyma (liver perfusion) and superior mesenteric vein (SMV) demonstrated a decreased peak density and a delayed peak in high-degree occlusion. The change rate of the area under the TDC of the liver and SMV decreased linearly as the degree of occlusion increased (PV, Y = -1.071*X + 106.8, r 2  = 0.972, P = 0.0003; liver, Y = -1.050*X + 101.8, r 2  = 0.933, P = 0.0017; SMV, Y = -0.985*X + 100.3, r 2  = 0.952, P = 0.0009). Dynamic 4D-CT revealed less severe IVC congestion during P-REBOA in haemorrhagic shock than in euvolemia. Analyses of TDC of the liver and SMV revealed a linear change in organ perfusion, regardless of intravascular volume., (© 2022. The Author(s).)

Introduction: Resuscitative endovascular balloon occlusion of the aorta (REBOA) causes a severe ischemia-reperfusion injury. Endovascular Perfusion Augmentation for Critical Care (EPACC) has emerged as a hemodynamic/mechanical adjunct to vasopressors and crystalloid for the treatment of post-REBOA ischemia-reperfusion injury. The objective of the study is to examine the impact of EPACC as a tool for a wean from complete REBOA compared to standard resuscitation techniques., Methods: Nine swine underwent anesthesia and then a controlled 30% blood volume hemorrhage with 30 min of supraceliac total aortic occlusion to create an ischemia-reperfusion injury. Animals were randomized to standardized critical care (SCC) or 90 min of EPACC followed by SCC. The critical care phase lasted 270 min after injury. Hemodynamic markers and laboratory values of ischemia were recorded., Results: During the first 90 min the intervention phase SCC spent 60% (54%-73%) and EPACC spent 91% (88%-92%) of the time avoiding proximal hypotension (<60 mm Hg), P = 0.03. There was also a statistically significant decrease in cumulative norepinephrine dose at the end of the experiment between SCC (80.89 mcg/kg) versus EPACC (22.03 mcg/kg), P = 0.03. Renal artery flow during EPACC was similar compared to SCC during EPACC, P = 0.19. But during the last hour of the experiment (after removal of aortic balloon) the renal artery flow in EPACC (2.9 mL/kg/min) was statistically significantly increased compared to SCC (1.57 mL/min/kg), P = 0.03. There was a statistically significant decrease in terminal creatinine in the EPACC (1.7 mg/dL) compared to SCC (2.1 mg/dL), P = 0.03., Conclusions: The 90 min of EPACC as a weaning adjunct in the setting of a severe ischemia-reperfusion injury after complete supraceliac REBOA provides improved renal flow with improvement in terminal creatinine compared to SCC with stabilized proximal hemodynamics and decreased vasopressor dose., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The understanding and management of hemorrhagic shock have evolved significantly over the last 400 years. Injured patients in shock mandate immediate surgeon involvement. Every graduating surgical resident and every surgeon taking trauma call should thoroughly understand the concepts of damage control resuscitation and be prepared to care for these patients. This review seeks to revisit the history of hemorrhagic shock and the evolution of damage control resuscitation.

Introduction: Trauma is the leading cause of death for those aged 1 to 46 years with most fatalities resulting from hemorrhage prior to arrival to hospital. Hemorrhagic shock patients receiving transfusion with 15 minutes experience lower mortality. Prehospital blood transfusion has many legal, fiduciary, and logistical issues. The San Antonio Fire Department participates in a consortium designed to enhance the stewardship of prehospital whole blood. This study aimed to stratify blood usage amongst the field supervisors and special operations units that carry whole blood. Methods: This was a 12-month retrospective analysis of blood usage. Blood tracking forms (used for either blood exchange of transfusion) were cross referenced with city financial records to determine blood usage patterns in the 7th Largest City in the US. We used descriptive statistics, compared usage ratios, and chi-square to compare dichotomized data. Results: A total of 363 whole blood units were obtained and 248 (68.3%) units of whole blood were transfused. EMS field supervisors transfused 74% of whole blood vs. 44% for special operations ambulances (p= <0.001). Response vehicles located in densely populated areas had the highest usage rates. All blood units were either transfused or returned for a zero blood unit wastage for expiration. Conclusion: The information contained within this work can provide other EMS agencies with a basic framework for comparison. The data from the SAFD's whole blood transfusion rate coupled with the clinical transfusion guideline has provided some insight for prospective agencies considering adopting a whole blood program. EMS systems and municipalities with similar characteristics can project their own whole blood needs and make informed decisions regarding program feasibility and design.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a damage control tool with a potential role in the hemodynamic resuscitation of severely ill patients in the civilian pre-hospital setting. REBOA ensures blood flow to vital organs by early proximal control of the source of bleeding. However, there is no consensus on the use of REBOA in the pre-hospital setting. This article aims to perform a systematic review of the literature about the feasibility, survival, indications, complications, and potential candidates for civilian pre-hospital REBOA., Methods: A literature search was conducted using Medline, EMBASE, LILACS and Web of Science databases. Primary outcome variables included overall survival and feasibility. Secondary outcome variables included complications and potential candidates for endovascular occlusion., Results: The search identified 8 articles. Five studies described the use of REBOA in pre-hospital settings, reporting a total of 47 patients in whom the procedure was attempted. Pre-hospital REBOA was feasible in 68-100% of trauma patients and 100% of non-traumatic patients with cardiac arrest. Survival rates and complications varied widely. Pre-hospital REBOA requires a coordinated and integrated emergency health care system with a well-trained and equipped team. The remaining three studies performed a retrospective analysis identifying 784 potential REBOA candidates., Conclusions: Pre-hospital REBOA could be a feasible intervention for a significant portion of severely ill patients in the civilian setting. However, the evidence is limited. The impact of pre-hospital REBOA should be assessed in future studies., (© 2022. The Author(s).)

Purpose: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) represents a minimally invasive technique of aortic occlusion (AO). It has been demonstrated to be safe and effective with appropriate training in traumatic hemorrhage with hemodynamic instability; however, its indications are still debated. The aim of this systematic review and meta-analysis is to assess the impact of REBOA on mortality in torso trauma patient with severe non-compressible hemorrhage compared to other temporizing hemostatic techniques., Study Design: The primary outcome is represented by 24-h, and in-hospital mortality. Secondary outcomes are post-procedural hemodynamic improvement (systolic blood pressure-SBP), mean injury severity score (ISS) differences, treatment-related morbidity, transfusional requirements and identification of prognostic factors., Results: A significant survival benefit at 24 h (RR 0.46; 95% CI 0.27-0.79; I 2 : 55%; p = 0.005) was highlighted in patients undergoing REBOA. Regarding in-hospital mortality (RR 0.99; 95% CI 0.75-1.32; I 2 : 73%; p = 0.98) no differences in risk of death were noticed. A hemodynamic improvement-although not significant-was highlighted, with 55.8 mmHg post-AO SBP mean difference between REBOA and control groups. A significantly lower mean number of packed Red Blood Cells (pRBCs) was noticed for REBOA patients (mean difference: - 3.02; 95% CI - 5.79 to - 0.25; p = 0.033). Nevertheless, an increased risk of post-procedural complications (RR 1.66; 95% CI 0.39-7.14; p = 0.496) was noticed in the REBOA group., Conclusions: REBOA may represent a valid tool in the initial treatment of multiple sites subdiaphragmatic hemorrhage with refractory hemodynamic instability. However, due to several important limitations of the present study, our findings should be interpreted with caution., Level of Evidence: Level III according to ELIS (SR/MA with up to two negative criteria)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

A focus of combat casualty care research is to develop treatments for when full resuscitation after hemorrhage is delayed. However, few animal models exist to investigate such treatments. Given the kidney's susceptibility to ischemia, we determined how delayed resuscitation affects renal function in a model of traumatic shock. Rats were randomized into three groups: resuscitation after 1 h (ETH-1) or 2 h (ETH-2) of extremity trauma and hemorrhagic shock, and sham control. ETH was induced in anesthetized rats with muscle injury and fibula fracture, followed by pressure-controlled hemorrhage [mean arterial pressure (MAP) = 55 mmHg] for 1 or 2 h. Rats were then resuscitated with whole blood until MAP stabilized between 90 and 100 mmHg for 30 min. MAP, glomerular filtration rate (GFR), creatinine, blood gases, and fractional excretion of sodium (nFENa + ) were measured for 3 days. Compared with control, ETH-1 and ETH-2 exhibited decreases in GFR and nFENa + , and increases in circulating lactate, creatinine, and blood urea nitrogen (BUN) before and within 30 min after resuscitation. The increases in creatinine, BUN, and potassium were greater in ETH-2 than in ETH-1, whereas lactate levels were similar between ETH-1 and ETH-2 before and after resuscitation. All measurements were normalized in ETH-1 within 2 days after resuscitation, with 22% mortality. However, ETH-2 exhibited a prolonged impairment of GFR, increased nFENa + , and a 66% mortality. Resuscitation 1 h after injury therefore preserves renal function, whereas further delay of resuscitation irreversibly impairs renal function and increases mortality. This animal model can be used to explore treatments for prolonged prehospital care following traumatic hemorrhage. NEW & NOTEWORTHY A focus of combat casualty care research is to develop treatment where full resuscitation after hemorrhage is delayed. However, animal models of combat-related hemorrhagic shock in which to determine physiological outcomes of such delays and explore potential treatment for golden hour extension are lacking. In this study, we filled this knowledge gap by establishing a traumatic shock model with reproducible development of AKI and shock-related complications determined by the time of resuscitation.

Background: Femur shaft fractures (FSF) are perceived as potentially life-threatening injuries due to significant blood loss. However, these injuries are rarely the sole cause of hemorrhagic shock. Clinical practice guidelines for the prehospital management of FSF are inconsistent, especially concerning the use and timing of traction splinting which is postulated to reduce bleeding. We sought to understand the association between FSF and shock, and identify risk factors for shock among casualties with FSF., Methods: This is a retrospective analysis of trauma casualties treated by Israeli Defense Forces (IDF) medical teams between the years 2000-2020 and suffering from isolated FSF. Prehospital data from the IDF-Medical Corps Trauma Registry was merged with hospitalization data from the Israeli National Trauma Registry. Isolated FSF was analyzed by excluding casualties with an Injury Severity Score ≥ 16 and an Abbreviated Injury Scale ≥ 3 in other anatomical regions. Shock was defined as systolic blood pressure ≤ 90 mmHg and/or heart rate ≥ 130 beats per minute. A case series review was performed for casualties in shock with isolated FSF injuries. Multivariable logistic regression was performed to assess for injury characteristics associated with shock., Results: During the study period, we identified 213 patients with FSF (4.9%) of which 129 were isolated injuries. Overall, 9.9% and 26.3% of casualties had concurrent thoracic and abdominal injuries, respectively. Most FSF were due to motor vehicle accidents (60.1%) and shock was present in 17.1%. In isolated FSF patients, gunshot and explosive injury mechanisms were prevalent (65.0%) with severe shock being present in 8.5%. Open fractures were present in 72.7% of isolated FSF patients in shock. Open FSF injuries were characterized by prehospital bleeding which was difficult to control. In a multivariable logistic regression model, severe concomitant injuries were associated with increased odds of shock., Conclusions: Shock rarely presents when FSF is the primary injury. Such casualties predominantly suffer from open FSF which may present as difficult to control thigh bleeding. Our findings do not support urgent prehospital leg traction splinting which may result in delayed evacuation to definitive care. Casualties with shock and FSF should be investigated for other sources of bleeding. Leg traction splinting should be reserved for suspected FSF injuries with shock or persistent thigh bleeding., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)