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The use of blood transfusion to treat hemorrhagic shock is a relatively new treatment with its origins in World War I. Due to the severity and nature of injuries seen, World War I provided the stimulus to propel medicine forward and accept whole blood transfusion for the trauma patient., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Civilian acute trauma care has advanced in recent decades; however, traumatic injury remains the leading cause of death in individuals aged 15 to 29 years in the United States and worldwide. Uncontrolled hemorrhage is the leading preventable cause of death in trauma patients, with up to half of these deaths occurring before reaching a medical facility. The timely application of hemorrhage control measures is critical to enhance the survivability of trauma patients and is one of the major challenges faced by medical providers in austere environments. The purpose of this review is to explore if early resuscitation with cold-stored whole blood therapy reduces the need for component therapy in the first 24 hours postinjury in the civilian population., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search in Medline, EMBASE, and Transfusion Evidence Library for studies reporting data on 24-hour blood product usage in trauma patients in hemorrhagic shock receiving initial therapy with whole blood. Two reviewers independently performed the selection of eligible studies., Results: Of a total of 2,150 identified studies, 11 studies (n = 4,792) met the inclusion criteria. There was heterogeneity in the study design, interventions, and outcomes. Seven studies reported a statistically significant decrease in 24-hour transfusion requirements in the whole blood intervention group in comparison with the control component therapy group. Three studies reported no significant difference between the two groups. One of the studies reported an increase in 24-hour transfusion requirements in the whole blood group., Conclusion: Overall, there appears to be a decrease in component therapy use following initial resuscitation with whole blood in trauma patients with hemorrhagic shock. However, further research is needed to address this important practical question (PROSPERO registration no. CRD42023422173)., Level of Evidence: Systematic Review; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Hemorrhagic shock (HS) is a life-threatening condition with high mortality rates despite current treatments. This study investigated whether targeted temperature management (TTM) could improve outcomes by modulating inflammation and protecting organs following HS. Using a rat model of HS, TTM was applied at 33°C and 36°C after fluid resuscitation. Surprisingly, TTM at 33°C increased mortality, while TTM at 36°C significantly improved survival rates. It also reduced histological damage in lung and kidney tissues, lowered serum lactate levels, and protected against apoptosis and excessive reactive oxygen species production. TTM at 36°C inhibited the release of high mobility group box 1 protein (HMGB1), a key mediator of inflammation, and decreased proinflammatory cytokine levels in the kidneys and lungs. Moreover, it influenced macrophage behavior, suppressing the harmful M1 phenotype while promoting the beneficial M2 polarization. Cytokine array analysis confirmed reduced levels of proinflammatory cytokines with TTM at 36°C. These results collectively highlight the potential of TTM at 36°C as a therapeutic approach to improve outcomes in HS. By addressing multiple aspects of injury and inflammation, including modulation of macrophage responses and cytokine profiles, TTM at 36°C offers promising implications for critical care management after HS, potentially reducing mortality and improving patient recovery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Abstract: Restoration of mesenteric lymphatic microcirculation is crucial for alleviating severe hemorrhagic shock-induced death. Exercise preconditioning (EP) enhances adaptability and resistance to injury and disease. The mitochondria-associated endoplasmic reticulum membrane (MAM) plays a crucial role in the energy and information exchange between the two organelles. Therefore, we hypothesized that EP ameliorates mesenteric lymphatic contractility through MAM in rats following hemorrhagic shock, aiming to confirm that EP enhances resistance to hemorrhagic shock and further popularizes the idea that exercise is beneficial for health. To test this hypothesis, we observed the effects of EP for 4 weeks on survival time and mesenteric lymphatic contractility in conscious rats following hemorrhagic shock and further explored the effects of MAM agonists and inhibitors. The results showed that EP prolonged the survival time and improved the mesenteric lymphatic contractility and reactivity in vivo and in vitro in rats underwent hemorrhagic shock, ameliorated the MAM ultrastructure in lymphatic smooth muscle cells (LSMCs) and reduced the voltage-dependent anion channel 1 (VDAC1, a vital protein of MAM) and IP3R1 expressions in mesenteric lymphatic tissue. Importantly, treatment with 2-APB (IP3R1 inhibitor) or VBIT-12 (VDAC1 inhibitor) prolonged the survival time, improved mesenteric lymphatic contractility in vivo , ameliorated the MAM ultrastructure injury, and decreased the IP3R1 or VDAC1 expressions in LSMCs in rats following hemorrhagic shock. In contrast, the administration of drinking water containing CdCl 2 (IP3R1 activator) abolished the beneficial effect of EP on hemorrhagic shock. Taken together, the protective effect of EP on lymphatic contractility following hemorrhagic shock was achieved by improving MAM in LSMCs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Introduction: Hemorrhage is a leading cause of death. Blood products are used for the treatment of hemorrhagic shock. The use of low titer group O whole blood (LTOWB) has become more common., Methods: Data from patients ≥15 years of age in the Trauma Quality Improvement Program (TQIP) database that received ≥10 units of packed red cells and/or LTOWB within the first 4-h of hospital arrival were included. The proportion of LTWOB of total blood products administered was correlated to 6- and 24-h mortality., Results: 12,763 met inclusion, 3827 (30 %) received LTOWB. On multivariable logistic regression (MVLR), there was no difference in survival at 6 h with a LTOWB. When assessing 24-h survival, there was improved survival with LTOWB ≥10 % (OR 1.18, 1.08-1.28)., Conclusions: In this analysis of TQIP data, patients receiving ≥10 units of PRBC or LTOWB, we found that higher proportions of LTOWB transfusion relative to the total volume of blood products transfused during the first 4 h were associated with improved 24-h, but not 6-h survival., Competing Interests: Declaration of competing interest ADF, MDA, FLW, MJC, TMG, and SGS have all received funding from the Department of Defense in the form of grants to their institution. We have no other conflicts of interest to report., (Published by Elsevier Inc.)

Introduction: Hemorrhagic shock requires immediate treatment to prevent mortality and organ dysfunction. This study evaluates the efficacy of methylene blue (MB) with blood transfusion (BT) as a potential rescue therapy in acute severe bleeding in pigs., Methods: Thirty animals were randomly assigned to one of six groups following the induction of fixed-pressure hemorrhagic shock, after reaching a mean arterial pressure (MAP) of 55 mmHg - Group 1 (60 BT: BT after 60 minutes), Group 2 (60 MB: MB infusion after 60 minutes), Group 3 (60 MB + BT: MB and BT after 60 minutes), Group 4 (15 MB + BT: MB and BT after 15 minutes), Group 5 (15 BT + 60 MB: BT after 15 minutes and MB infusion after 60 minutes), and Group 6 (15 MB + 60 BT: MB infusion after 15 minutes and BT after 60 minutes). Hemodynamic and blood gas parameters were meticulously recorded, reversal of the shock was considered when MAP reached 90% of the baseline MAP., Results: Except for Group 2, all groups reverted from the shock. However, groups that received MB in combination with BT, specifically Groups 3 and 4, exhibited statistically significant higher ratios of maximum MAP to baseline MAP., Conclusion: Using MB concomitant with BT allowed the reversal of hemorrhagic shock with higher median arterial pressure levels compared to BT alone or applying MB separately from BT. This suggests that simultaneous application of MB and BT could be a more effective strategy for reversing the effects of severe acute bleeding.

Background: Current epidemiological diagnostic criteria for hemorrhagic shock and encephalopathy syndrome (HSES) may not be optimal for early identification in clinical settings. We analyzed the specific timing at which Bacon's criteria were met after encephalopathy onset., Methods: This retrospective observational study was conducted at the National Center for Child Health and Development, a quaternary-care facility that receives critically ill patients from a wide geographic area, between January 2014 and December 2023. Cases of HSES were identified using Bacon's criteria. Data on detailed time courses after seizure onset were extracted from medical records. The primary outcome was the time at which Bacon's criteria were met, measured using median values., Results: Of the 206 patients with acute encephalopathy, 13 had HSES. Four were excluded due to insufficient data. Only one patient met Bacon's criteria based on initial examinations, while eight met them after presentation. The median time from seizure onset to meeting Bacon's criteria was 4 h. Early diagnostic markers included abnormal blood coagulation, renal dysfunction, and elevated enzyme levels. The median time to initiation of steroid pulse therapy was 11.5 h; it was 9 h for plasma exchange. Irreversible brain damage, indicated by cerebral edema, occurred at a median of 7 h post-seizure., Conclusions: The existing criteria fail in the context of early diagnosis. Routine practice should include early blood tests, including those for coagulation abnormalities, for patients with febrile status epilepticus to identify HSES at an early stage. Future research should validate new diagnostic criteria and explore additional interventions., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rapid and effective tourniquet application is crucial in life-threatening limb hemorrhage to minimize mortality. However, the widespread availability of counterfeit tourniquets is a growing concern, as these devices may lack essential quality control measures, potentially compromising patient care. We describe one case where the delayed mechanical failure of a Combat Application Tourniquet (CAT)-like tourniquet caused the death of a Ukrainian soldier during evacuation to an urban trauma center. In April 2022, a 19-year-old male underwent a bilateral below-the-knee amputation from an antipersonnel landmine. Massive hemorrhage prompted the use of bilateral CAT-like tourniquets. During transportation, the right tourniquet's windlass broke, resulting in a brisk hemorrhage. Due to the high patient-to-healthcare-personnel ratio, the bleeding remained unaddressed for an unknown amount of time, resulting in death from hemorrhagic shock. This study underscores the need for robust quality control measures and the establishment of strict regulations against deploying counterfeit tourniquets to avoid preventable deaths., Competing Interests: The authors do not have any conflicts of interest to disclose., (2024.)

Low-titer O-positive whole blood was used extensively by the military during operations in Iraq and Afghanistan. Studies have consistently shown that this therapy is feasible, safe, and effective in the management of hemorrhagic shock in trauma patients, and it is now the standard of care across the US military Joint Trauma System. The military's success in using low-titer O-positive whole blood has renewed the practice in the civilian setting, with recent research confirming its safety and efficacy. In a few short years, use of this treatment for hemorrhagic shock has expanded to more than 80 US level I and level II trauma centers. However, its use is still relatively rare in the rural hospital setting. This article describes the benefits for patients, staff members, and the overall trauma system of using low-titer O-positive whole blood in rural hospitals., (©2024 American Association of Critical-Care Nurses.)

Introduction: Hemorrhagic shock (HS) poses a life-threatening condition with the lungs being one of the most susceptible organs to its deleterious effects. Extracellular cold-inducible RNA binding protein has emerged as a pivotal mediator of inflammation, and its release has been observed as a case of HS-induced tissue injury. Previous studies unveiled a promising engineered microRNA, designated PS-OMe miR130, which inhibits extracellular cold-inducible RNA binding protein, thereby safeguarding vital organs. In this study, we hypothesized that PS-OMe miR130 serves as a protective shield against HS-induced lung injury by curtailing the overzealous inflammatory immune response., Methods: Hemorrhagic shock was induced in male C57BL6 mice by withdrawing blood via a femoral artery cannula to a mean arterial pressure of 30 mm Hg for 90 minutes. The mice were resuscitated with twice the shed blood volume with Ringer's lactate solution. They were then treated intravenously with either phosphate-buffered saline (vehicle) or 62.5 nmol PS-OMe miR130. At 4 hours later, blood and lungs were harvested., Results: Following PS-OMe miR130 treatment in HS mice, a substantial decrease was observed in serum injury markers including aspartate aminotransferase, alanine transaminase, lactate dehydrogenase, and blood urea nitrogen. Serum interleukin (IL)-6 exhibited a similar reduction. In lung tissues, PS-OMe miR130 led to a significant decrease in the messenger RNA expressions of pro-inflammatory cytokines (IL-6, IL-1β, and tumor necrosis factor α), chemokines (keratinocyte-derived chemokine and macrophage inflammatory protein 2), and an endothelial injury marker, E-selectin. PS-OMe miR130 also produced substantial inhibition of lung myeloperoxidase activity and resulted in a marked reduction in lung injury as evidenced by histological evaluation. This was further confirmed by the observation that PS-OMe miR130 significantly reduced the presence of lymphocyte antigen 6 family member G-positive neutrophils and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic cells., Conclusion: PS-OMe miR130 emerges as a potent safeguard against HS-induced lung injury by effectively inhibiting pro-inflammation and injuries, offering a promising therapeutic strategy in such critical clinical condition., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Percutaneous endoscopic gastrostomy (PEG) is widely used for long-term enteral nutrition in patients unable to maintain adequate oral intake. Despite advancements in PEG techniques, complications remain a concern. We report a case of a 94-year-old bedridden man who developed significant complications after PEG placement using the pull method. Initially, minor bleeding at the puncture site was managed using traction compression. However, the patient later experienced hemorrhagic shock owing to pulsatile bleeding around the gastrostomy site. Despite attempts to control the bleeding through traction and transfusions, a pseudoaneurysm adjacent to the PEG button was identified. The patient underwent successful transcatheter arterial embolization (TAE). Post-TAE, no further bleeding or hematoma was observed, and imaging confirmed the resolution of the pseudoaneurysm and hematoma. Methicillin-resistant Staphylococcus aureus (MRSA) infection was detected at the gastrostomy site, which contributed to complications. Despite successful management of the bleeding, the patient's overall condition deteriorated, and he died on postoperative day 66. This case underscores the importance of vigilant monitoring and management of PEG-related complications, particularly infections that may precipitate severe vascular events., (© 2024. Japanese Society of Gastroenterology.)

Hemorrhagic shock and subsequent resuscitation can cause significant dysregulation of critical systems, including the vascular endothelium. Following hemorrhage, the endothelial lining (glycocalyx) can shed, causing release of glycocalyx components, endothelial activation, and systemic inflammation. A canine model of hemorrhagic shock was used to evaluate five resuscitation fluids, including Lactated Ringers+Hetastarch, Whole Blood (WB), Fresh Frozen Plasma+packed Red Blood Cells (FFP+pRBC), and two hemoglobin-based oxygen carrier (HBOC) fluids, for their impact on glycocalyx shedding. Under anesthesia, purpose-bred adult canines were instrumented and subjected to a controlled hemorrhage with blood being drawn until a mean arterial pressure of <50 mmHg was reached or 40 % of the estimated blood volume was removed. Canines were left in shock for 45 mins before being resuscitated with one of the resuscitation fluids over 30 mins. Following resuscitation, the dogs were monitored up to 2 weeks. Following an additional 3-4 weeks for washout, the canines repeated the protocol, undergoing each resuscitation fluid individually. Blood samples were collected during each round at various timepoints for serum isolation, which was used for detection of glycocalyx biomarker. Comparison of baseline and post-hemorrhage alone showed a significant reduction in serum protein (p<0.0001), heparan sulfate (p<0.001), and syndecan-1 (p<0.0001) concentrations, and a significant increase in hyaluronan (p<0.0001) concentration. Intercomparisons of resuscitation fluids indicated minimal differences in glycocalyx markers over time. Comparisons within each fluid showed dynamic responses in glycocalyx biomarkers over time. Relative to individual baselines, syndecan-1 was significantly reduced after resuscitation in most cases (p<0.0001), excluding WB and FFP+pRBC. In all cases, VE-cadherin was significantly elevated at 24 hr compared to baseline (p<0.001). Hyaluronan was significantly elevated by 3 hr in all cases (p<0.01), except for HBOC fluids. Total glycosaminoglycans were significantly reduced only at 3 hr (p<0.001) for non-HBOC fluids. Similarly, heparan sulfate was significantly reduced with all fluids between resuscitation and 24 hr (p<0.01), except WB. The temporal changes in canine glycocalyx biomarkers were atypical of hemorrhage response in other species. This suggests that the hemorrhage lacked severity and/or typical glycocalyx biomarkers do not reflect the canine endothelium compared to other species. Further research is needed to characterize the canine endothelium and the response to resuscitation fluids., Competing Interests: Declaration of Competing Interest None to disclose., (Published by Elsevier Ltd.)

Abstract: The past century has seen many advances in the field of resuscitation. This is particularly true in the subset of patients who sustain major injuries causing hemorrhagic shock (HS) and require massive transfusion of more than 10 U of blood within the first 24 hours. Controversies on how best to resuscitate these patients include the role of fresh whole blood, stored whole blood, fresh frozen plasma, platelets, colloid solutions, balanced electrolytes solution, vasopressors, and diuretics. This review summarizes the often-contradictory recommendations observed and studied by a single trauma surgeon working in a busy urban acute care center for 65 years., Level of Evidence: Level I., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: French prehospital military medical teams are provided with labile blood products to effectively address hemorrhagic shock. In combat environment, standard good medical practice may limit efficacy of therapeutic goals regarding damage control resuscitation., Study Design and Methods: We present here a case report describing the management of a soldier heavily wounded during a helicopter forward medical evacuation in Sahel region., Results: We report the challenge encountered by medical team using only a humeral intraosseous route available due to severity of lesions and challenging environment. In this configuration, multi-lumen extender enabled transfusion of two units of packed red blood cells and two units of plasma, and analgesia while limiting manipulation and dislodgment of the fragile intraosseous route. This situation, outside of usual good medical practice, raises issues of hemolysis, physicochemical compability of drugs and blood products, and consequences on flow rate reduction., Discussion: With this case, we emphasize the benefit of multi-lumen extender associated with intraosseous route for early management of heavy casualties in harsh prehospital environment. Literature suggests that hemolysis and physicochemical compability should remain limited. The main issue of this setting consists of flow reduction and can be addressed by prioritizing humeral route, and using counter pressure cuffs, until a second peripheral or central line is available and management can resume without the need for multi-lumen extender., (© 2024 AABB.)

Background: Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors for acute kidney injury after severe trauma; however, the effects of the combination of RM and HS on kidney function are unknown. The purpose of this study was to determine the impact of RM and HS on renal function, oxygenation, perfusion, and morphology in a pig model., Methods: Forty-seven female pigs were divided into five groups: sham, RM, HS, HS and moderate RM (RM4/HS), and HS and severe RM (RM8/HS). Rhabdomyolysis was induced by intramuscular injection of glycerol 50% with a moderate dose (4 ml/kg for the RM4/HS group) or a high dose (8 ml/kg for the RM and RM8/HS groups). Among animals with HS, after 90 min of hemorrhage, animals were resuscitated with fluid followed by transfusion of the withdrawn blood. Animals were followed for 48 h. Macro- and microcirculatory parameters measurements were performed., Results: RM alone induced a decrease in creatinine clearance at 48 h (19 [0 to 41] vs. 102 [56 to 116] ml/min for RM and sham, respectively; P = 0.0006) without alteration in renal perfusion and oxygenation. Hemorrhagic shock alone impaired temporarily renal microcirculation, function, and oxygenation that were restored with fluid resuscitation. The RM4/HS and RM8/HS groups induced greater impairment of renal microcirculation and function than HS alone at the end of blood spoliation that was not improved by fluid resuscitation. Mortality was increased in the RM8/HS and RM4/HS groups in the first 48 h (73% vs. 56% vs. 9% for the RM8/HS, RM4/HS, and HS groups, respectively)., Conclusions: The combination of HS and RM induced an early deleterious effect on renal microcirculation, function, and oxygenation with decreased response to resuscitation and transfusion compared with HS or RM alone., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Abstract: Purpose: To evaluate the dose-dependent effect of whole blood (WB) on the outcomes of civilian trauma patients with hemorrhagic shock. Methods: We performed a 2-year (2020-2021) retrospective analysis of the ACS-TQIP dataset. Adult (≥18) trauma patients with a shock index (SI) >1 who received at least 5 units of PRBC and one unit of WB within the first 4 h of admission were included. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications and hospital and intensive care unit length of stay. Results: A total of 830 trauma patients with a mean (SD) age of 38 (16) were identified. The median [IQR] 4-h WB and PRBC requirements were 2 [2-4] U and 10 [7-15] U, respectively, with a median WB:RBC ratio of 0.2 [0.1-0.3]. Every 0.1 increase in WB:RBC ratio was associated with decreased odds of 24-h mortality (aOR: 0.916, P = 0.035) and in-hospital mortality (aOR: 0.878, P < 0.001). Youden's index identified 0.25 (1 U of WB for every 4 U of PRBC) as the optimal WB:PRBC ratio to reduce 24-h mortality. High ratio (≥0.25) group had lower adjusted odds of 24-h mortality (aOR: 0.678, P = 0.021) and in-hospital mortality (aOR: 0.618, P < 0.001) compared to the low ratio group. Conclusions: A higher WB:PRBC ratio was associated with improved early and late mortality in trauma patients with hemorrhagic shock. Given the availability of WB in trauma centers across the United States, at least one unit of WB for every 4 units of packed red blood cells may be administered to improve the survival of hemorrhaging civilian trauma patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

This study aimed to modify a laser Doppler flowmeter designed and assembled at our institute. After measuring sensitivity evaluation in ex vivo experiments, we confirmed the efficacy of this new device for monitoring real-time esophageal mucosal blood flow changes after thoracic stent graft implantation by simulating various clinical situations in an animal model. Thoracic stent graft implantation was performed in a swine model (n = 8). Esophageal mucosal blood flow decreased significantly from baseline (34.1 ± 18.8 ml/min/100 g vs. 16.7 ± 6.6 ml/min/100 g, P < 0.05) in the lower esophagus (Th6-Th8) where the stent graft covered the aorta. In the hemorrhagic shock model (shock index ≥ 1.0), esophageal mucosal blood flow showed a remarkable change from baseline in the upper esophagus (Th1-Th3), where the stent graft did not cover the aorta (20.8 ± 9.8 ml/min/100 g vs. 12.9 ± 8.6 ml/min/100 g, P < 0.01); however, it returned to the baseline value within a 30-min period. Mucosal blood flow remained stable in the esophagus, where the stent graft did not cover the aorta. After elevating the mean blood pressure to > 70 mmHg with continuous intravenous noradrenaline infusion, esophageal mucosal blood flow increased significantly in both regions; however, the reaction was different between the two regions. Our newly developed laser Doppler flowmeter could measure real-time esophageal mucosal blood flow changes in various clinical situations during thoracic stent graft implantation in a swine model. Hence, this device can be applied in many medical fields by downsizing it., (© 2023. The Japanese Society for Artificial Organs.)

A 42-year-old male patient experienced hemorrhagic shock after endotracheal intubation. Emergency gastroscopy showed no upper gastrointestinal bleeding, but active tracheal bleeding. After sedation, the tracheal bleeding was successfully stopped with gastroscopy. Post-intubation airway bleeding is a rare but fatal adverse event, and finding the exact bleeding site and quickly stopping the bleeding is the key to successful treatment.

Objective: Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H 2 S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H 2 S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl-d-Aspartate (NMDA) receptor function., Methods: Mice were immediately administered dl-propargylglycine (PAG) intragastrically as an H 2 S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala., Results: Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H 2 S-induced intestinal and cerebral injury., Conclusion: This experimental data suggests that H 2 S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The objective of this study was to test the therapeutic effect of carbon monoxide polyhemoglobin (polyCOHb) in haemorrhagic shock/resuscitation and its underlying mechanisms., Methods: 48 rats were divided into two experimental parts, and 36 rats in the first experiment and 12 rats in the second experiment. In the first experimental part, 36 animals were randomly assigned to the following groups: hydroxyethyl starch group (HES group, n  = 12), polyhemoglobin group (polyHb group, n  = 12), and carbon monoxide polyhemoglobin group (polyCOHb group, n  = 12). In the second experimental part, 12 animals were randomly assigned to the following groups: polyHb group ( n  = 6), and polyCOHb group ( n  = 6). Then the anaesthetised rats were haemorrhaged by withdrawing 50% of the animal's blood volume (BV), and resuscitated to the same volume of the animal's withdrawing BV with HES, polyHb, polyCOHb. In the first experimental part, the 72h survival rates of each groups animals were measured. In the second experimental part, the rats' mean arterial pressure (MAP), heart rate (HR), blood gas levels and other indicators were dynamically monitored in baseline, haemorrhagic shock (HS), at 0point resuscitation (RS 0h) and after 1 h resuscitation (RS 1h). The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by ELISA kits in both groups of rats at RS 1h. Changes in pathological sections were examined by haematoxylin-eosin (HE) staining. Nuclear factor erythroid 2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) levels were detected by immunohistochemical analysis, while myeloperoxidase (MPO) levels were detected by immunofluorescence. DHE staining was used to determine reactive oxygen species (ROS) levels., Results: The 72h survival rates of the polyHb and polyCOHb groups were 50.00% (6/12) and 58.33% (7/12) respectively, which were significantly higher than that of the 8.33% (1/12) in the HES group ( p  < 0.05). At RS 0h and RS 1h, the HbCO content of rats in the polyCOHb group (1.90 ± 0.21, 0.80 ± 0.21) g/L were higher than those in the polyHb group (0.40 ± 0.09, 0.50 ± 0.12)g/L ( p  < 0.05); At RS 1h, the MDA (41.47 ± 3.89 vs 34.17 ± 3.87 nmol/ml) in the plasma, Nrf2 and HO-1 content in the colon of rats in the polyCOHb group were lower than the polyHb group. And the SOD in the plasma (605.01 ± 24.46 vs 678.64 ± 36.37) U/mg and colon (115.72 ± 21.17 vs 156.70 ± 21.34) U/mg and the MPO content in the colon in the polyCOHb group were higher than the polyHb group ( p  < 0.05)., Conclusions: In these haemorrhagic shock/resuscitation models, both polyCOHb and polyHb show similar therapeutic effects, and polyCOHb has more effective effects in maintaining MAP, correcting acidosis, reducing inflammatory responses than that in polyHb.

Introduction: Non-compressible torso hemorrhagic (NCTH) shock is the leading cause of potentially survivable trauma on the battlefield. New hypotensive drug therapies are urgently required to resuscitate and protect the heart and brain following NCTH. Our aim was to examine the strengths and limitations of permissive hypotension and discuss the development of small-volume adenosine, lidocaine, and Mg2+ (ALM) fluid resuscitation in rats and pigs., Materials and Methods: For review of permissive hypotension, a literature search was performed from inception up to November 2023 using PubMed, Cochrane, and Embase databases, with inclusion of animal studies, clinical trials and reviews with military and clinical relevance. For the preclinical study, adult female pigs underwent laparoscopic liver resection. After 30 minutes of bleeding, animals were resuscitated with 4 mL/kg 3% NaCl ± ALM bolus followed 60 minutes later with 4 h 3 mL/kg/h 0.9% NaCl ± ALM drip (n = 10 per group), then blood transfusion. Mean arterial pressure (MAP) and cardiac output (CO) were continuously measured via a left ventricular pressure catheter and pulmonary artery catheter, respectively. Systemic vascular resistance (SVR) was calculated using the formula: 80 × (MAP - CVP)/CI. Oxygen delivery was calculated as the product of CO and arterial oxygen content., Results: Targeting a MAP of ∼50 mmHg can be harmful or beneficial, depending on how CO and SVR are regulated. A theoretical example shows that for the same MAP of 50 mmHg, a higher CO and lower SVR can lead to a nearly 2-fold increase in O2 supply. We further show that in animal models of NCTH, 3% NaCl ALM bolus and 0.9% NaCl ALM drip induce a hypotensive, high flow, vasodilatory state with maintained tissue O2 supply and neuroprotection. ALM therapy increases survival by resuscitating the heart, reducing internal bleeding by correcting coagulopathy, and decreasing secondary injury., Conclusions: In rat and pig models of NCTH, small-volume ALM therapy resuscitates at hypotensive pressures by increasing CO and reducing SVR. This strategy is associated with heart and brain protection and maintained tissue O2 delivery. Translational studies are required to determine reproducibility and optimal component dosing. ALM therapy may find wide utility in prehospital and far-forward military environments., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Introduction: Achieving simultaneous cerebral blood flow (CBF) and oxygenation measures, specifically for point-of-care injury monitoring in prolonged field care, requires the implementation of appropriate methodologies and advanced medical device design, development, and evaluation. The near-infrared spectroscopy (NIRS) method measures the absorbance of light whose attenuation is related to cerebral blood volume and oxygenation. By contrast, diffuse correlation spectroscopy (DCS) allows continuous noninvasive monitoring of microvascular blood flow by directly measuring the degree of light scattering because of red blood cell (RBC) movement in tissue capillaries. Hence, this study utilizes these two optical approaches (DCS-NIRS) to obtain a more complete hemodynamic monitoring by providing cerebral microvascular blood flow, hemoglobin oxygenation and deoxygenation in hemorrhage, and hypoxia-induced injuries., Materials and Methods: Piglet models of hemorrhage and hypoxia-induced brain injury were used with DCS and NIRS sensors placed over the preorbital to temporal skull regions. To induce hemorrhagic shock, up to 70% of the animal's total blood volume was withdrawn through graded hemorrhage serially via a syringe from a femoral artery cannula in 10 mL/kg aliquots over 1 minute every 10 minutes. A second group of animals was subjected to hypoxia for ∼1 hour through graded hypoxia by serial titration from normoxic fraction inspired oxygen of 21% to hypoxic fraction inspired oxygen of 6%. A subset of animals served as sham-controls undergoing anesthesia, instrumentation, and ventilation as the injury groups, yet experiencing no blood loss or hypoxia., Results: We first investigated the relationship between hemorrhagic shock and no shock by using measured biomarkers, including blood flow index from DCS associated with CBF and oxygenated (HbO) and de-oxygenated hemoglobin from NIRS. The statistical analysis revealed a significant difference between no shock and hemorrhagic shock (P < .01). The HbO decreased with each blood loss as expected, yet the de-oxygenated hemoglobin was slightly changed. During hypoxia-induced global hypoxic-ischemic injury tests, the CBF results from graded hypoxia were consistent with the response previously measured during hemorrhagic shock. Moreover, HbO decreased when the animal was hypoxic, as expected. A statistical analysis was also conducted to compare the results with those of the sham controls., Conclusions: There is a consistency in blood flow measures in both injury mechanisms (hemorrhagic shock and hypoxia), which is significant as the new prototype system provides similar measures and trends for each brain injury type, suggesting that the optical system can be used in response to different injury mechanisms. Notably, the results support the idea that this optical system can probe the hemodynamic status of local cerebral cortical tissue and provide insight into the underlying changes of cerebral tissue perfusion at the microvascular level. These measurement capabilities can improve shock identification and monitoring of medical management of injuries, particularly hemorrhagic shock, in prolonged field care., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Introduction: Many trauma patients die from hemorrhagic shock in the military and civilian settings. Although two-thirds of hemorrhagic shock victims die of reasons other than exsanguination, such as the consequent cytokine storm, anti-inflammatory therapies failed to be utilized. Apoptotic cell-based treatments enhance innate ability to exert systemic immunomodulation as demonstrated in several clinical applications and hence might present a novel approach in hemorrhagic shock treatment., Materials and Methods: Twenty-two rats underwent a pressure-controlled hemorrhagic shock model and followed up for 24 hours. An infusion of apoptotic cells (Allocetra-OTS, Enlivex Therapeutics Ltd, Nes Ziona, Israel) was administered to the treatment group. Hemodynamics, blood counts, biochemistry findings, and cytokine profile were compared to a saline-resuscitated control group., Results: The treatment group's mean arterial pressure decreased from 94.8 mmHg to 28.2 mmHg, resulting in an 8.13 mg/dL increase in lactate and a 1.9 g/L decrease in hemoglobin, similar to the control group. White blood cells and platelets decreased more profoundly in the treatment group. A similar cytokine profile after 24 hours was markedly attenuated in the treatment group 2 hours after bleeding. Levels of pro-inflammatory cytokines such as interleukin (IL)-1a (28.4 pg/mL vs. 179.1 pg/mL), IL-1b (47.4 pg/mL vs. 103.9 pg/mL), IL-6 (526.2 pg/mL vs. 3492 pg/mL), interferon γ (11.4 pg/mL vs. 427.9 pg/mL), and tumor necrosis factor α (19.0 pg/mL vs. 31.7 pg/mL) were profoundly lower in the treatment group., Conclusion: In a pressure-control hemorrhagic shock model in rats, apoptotic cell infusion showed preliminary signs of a uniform attenuated cytokine response. Apoptotic cell-based therapies might serve as a novel immunomodulatory therapy for hemorrhagic shock., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Purpose: Hypocalcemia is associated with increased mortality in trauma patients with hemorrhagic shock who require massive transfusion protocols (MTPs). Despite known risks of potentiating hypocalcemia with blood product administration, there is little research discussing appropriate calcium replacement. The purpose of this study was to evaluate the ability of a standardized calcium replacement protocol to reduce the incidence of hypocalcemia in trauma patients undergoing MTP., Methods: This retrospective, single-center, pre-post study evaluated the use of a calcium replacement protocol during MTP. Adult trauma patients with MTP orders who received at least one "round" of product transfusion were included. Patients were excluded if their ionized calcium (iCa) levels were unavailable or they were transferred to a higher level of care within 4 hours of presentation. The primary outcome was incidence of hypocalcemia (iCa of <1.1 mg/dL) within 24 hours of MTP initiation. Secondary endpoints included the incidence of severe hypocalcemia (iCa of <0.9 mg/dL), time to first calcium dose, total calcium dose administered (mEq), resolution of hypocalcemia within 24 hours, hypercalcemia, adherence to the calcium replacement protocol, and mortality., Results: The incidence of hypocalcemia within 24 hours was significantly lower in the postprotocol group (63% vs 95.2%; P = 0.006). There was not a significant difference in the incidence of severe hypocalcemia between the groups (39.1% vs 69.1%; P = 0.083). Time to first calcium dose was significantly shorter in postprotocol patients compared to preprotocol patients (median [interquartile range], 5.5 [0-21] minutes vs 43 [22.8-73] minutes; P < 0.0001), and postprotocol patients were administered more calcium during MTP (40.8 [27.2-54.4] mEq vs 27.2 [14-32.2] mEq; P = 0.005). Adherence to the protocol was seen in only 37% of patients in the postprotocol group. There was no difference in the rate of adverse events or overall mortality., Conclusion: Trauma patients who received massive transfusion of blood products had a significantly lower incidence of hypocalcemia after a calcium replacement protocol was implemented., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: This study aimed to utilize a hemorrhagic shock pig model to compare two hemodynamic monitoring methods, pulse index continuous cardiac output (PiCCO) and spectral carotid artery Doppler ultrasound (CDU). Additionally, we sought to explore the feasibility of employing CDU as a non-invasive hemodynamic monitoring tool in the context of hemorrhagic shock and fluid resuscitation., Design: Animal experiments., Setting and Subjects: Female pigs were selected, and hemorrhagic shock was induced by rapid bleeding through an arterial sheath., Interventions: Hemodynamic monitoring was conducted using both PiCCO and CDU during episodes of hemorrhagic shock and fluid resuscitation., Measurements and Main Results: Among the 10 female pigs studied, CDU measurements revealed a significant decrease in carotid velocity time integral (cVTI) compared to baseline values under shock conditions. During the resuscitation phase, after the mean arterial pressure (MAP) returned to its baseline level, there was no significant difference between cVTI and baseline values. A similar trend was observed for carotid peak velocity (cPV). The corrected flow time (FTc) exhibited a significant difference only at the time of shock compared to baseline values. In comparison to PiCCO, there was a significant correlation between cVTI and MAP (r = 0.616, P < 0.001), stroke volume (SV) (r = 0.821, P < 0.001), and cardiac index (CI) (r = 0.698, P < 0.001). The carotid Doppler shock index (cDSI) displayed negative correlations with MAP (r =  - 0.593, P < 0.001), SV (r =  - 0.761, P < 0.001), and CI (r =  - 0.548, P < 0.001), while showing a positive correlation with the shock index (SI) (r = 0.647, P < 0.001)., Conclusions: Compared to PiCCO, CDU monitoring can reliably reflect the volume status of hemorrhagic shock and fluid resuscitation. CDU offers the advantages of being non-invasive, providing real-time data, and being operationally straightforward. These characteristics make it a valuable tool for assessing and managing hemorrhagic shock, especially in resource-limited settings., (© 2024. The Author(s).)

Background: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available., Methods: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product., Results: At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01)., Conclusion: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “œwork of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

This study aims to reveal the metabolic differences between SDC-1 knockout mice and wild-type mice and the metabolic differences caused by shock in SDC-1 knockout mice by integrating transcriptomics and metabolomics. A total of 1009 differential metabolites were differentially expressed based on untargeted metabolomics and high-resolution mass spectrometry detection techniques. According to Kyoto Encyclopedia of Genes and Genomes enrichment, SDC-1 knockout significantly altered fat digestion and absorption, GnRH signaling pathway, fructose and mannose metabolism, and some other amino-related metabolic pathways and significantly modulated positively regulated longevity regulatory pathways, longevity regulatory pathways-worm, nicotinamide and niacinamide metabolism, and vitamin digestion and absorption pathways after its shock. Our findings indicate that SDC-1 knockout may have potential therapeutic effects in hemorrhagic shock by increasing nicotinamide metabolism., (© 2023. The Author(s).)

Introduction: Along with recent advances in analytical technologies, tricarboxylic acid-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock. For traumatized patients, the knowledge of the role of lipid oxidation substrates is sparse. In this study, we aimed to analyze the dynamics of systemic acylcarnitine (AcCa) release in a standardized polytrauma model with hemorrhagic shock., Methods: Fifty-two male pigs (50 ± 5 kg) were randomized into two groups: group isolated fracture was subject to a standardized femur shaft fracture, and group polytrauma was subject to a femur fracture, followed by blunt chest trauma, liver laceration, and a pressure-controlled hemorrhagic shock for 60 minutes. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at six time points (baseline, trauma, resuscitation, 2 hours, 4 hours, and 6 hours). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements of tissue perfusion. Longitudinal analyses were performed with linear mixed models, and Spearman's correlations were calculated. A p value of 0.05 was defined as threshold for statistical significance., Results: From a total of 303 distinct lipids, we identified two species of long-chain AcCas. Both showed a highly significant ( p < 0.001) twofold increase after hemorrhagic shock in group polytrauma that promptly normalized after resuscitation. This increase was associated with a significant decrease of the base excess ( p = 0.005), but recovery after resuscitation was faster. For both AcCas, there were significant correlations with decreased muscle tissue oxygen delivery ( p = 0.008, p = 0.003) and significant time-lagged correlations with the increase of creatine kinase ( p < 0.001, p < 0.001)., Conclusion: Our results point to plasma AcCas as a possible indicator for mitochondrial dysfunction and cellular ischemia in hemorrhagic shock. The more rapid normalization after resuscitation in comparison with acid base changes may warrant further investigation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Early resuscitation using blood products is critical for patients with severe hemorrhagic shock. We aimed to develop and validate a new scoring system, hemorrhagic shock transfusion prediction (HSTP) score, to predict the need for massive transfusion (MT) in these patients, compared to the widely used Assessment of Blood Consumption (ABC) score. Trauma patients admitted to Emtiaz Hospital in Iran from 2017 to 2021 were retrospectively included. Patients assigned a code 1 or 2 according to the Emergency severity index (ESI) triage system have been divided into MT and non-MT groups. MT was defined as receiving ≥ 10 units of packed cells (PCs) in 24 h. Demographic information, admission vital signs, and lab results available within 15 min were compared between the groups. A new predictive score was developed using logistic regression of statistically significant parameters. Out of 1029 patients, 651 (63.3%) required MT. An arrival, diastolic blood pressure < 79.5 mm Hg, absolute lymphocyte count > 1850/μL, base excess < - 4.25, and blood glucose > 156 mg/dL were independent predictors included in the HSTP score. The sensitivity and specificity were 74.36% and 53.87% for the HSTP score, compared to 31.03% and 76.16% for the ABC score. Moreover, the positive and negative predictive values were 77.88% and 49.03% for the HSTP score, versus 74.15% and 33.66% for ABC. The new scoring system demonstrated higher sensitivity and improved positive and negative predictive values compared to the ABC score. This score can assist physicians in making accurate transfusion decisions quickly, but further prospective studies are warranted to validate its clinical utility., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Abstract: This review describes the necessity, evolution, and current state of prehospital blood programs in the United States. Less than 1% of 9-1-1 ground emergency medical service agencies have been able to successfully implement prehospital blood transfusions as part of a resuscitation strategy for patients in hemorrhagic shock despite estimates that annually between 54,000 and 900,000 patients may benefit from its use. The use of prehospital blood transfusions as a tool for managing hemorrhagic shock has barriers to overcome to ensure it becomes widely available to patients throughout the United States. Barriers include (1) current state Emergency Medical Services clinicians' scope of practice limitations; (2) program costs and reimbursement of blood products; (3) no centralized data collection process for prehospital hemorrhagic shock and patient outcomes; (4) collaboration between prehospital agencies, blood suppliers, and hospital clinicians and transfusion service activities. The following article identifies barriers and a proposed roadmap to reduce death due to prehospital hemorrhage., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Background: Uncontrolled hemorrhagic shock is a leading cause of early death after injury. Resuscitative endovascular balloon occlusion of the aorta (REBOA) represents a paradigm shift in achieving hemodynamic stability and its implementation still remain controversial in different settings. The recently published UK-REBOA Randomized Clinical Trial aimed to determine the effectiveness of REBOA in patients with hemorrhagic shock, concluding its increased mortality compared with standard care alone., Methods: An adjustment of the statistical analysis was performed and a comprehensive analysis was proposed to address the study's limitations and demonstrate that these conclusions cannot be considered as benchmarks., Results: Primary and secondary outcomes were analyzed using Bayesian logistic regression and generalized linear models suitable for the outcome distribution. No statistically significant differences were observed between the two groups for the primary outcome (p-value 0.3341) nor in most of the secondary outcomes. The results of the principal stratum analyses (to account for intercurrent events) also did not show significant differences after the statistical analysis tests., Conclusion: It cannot be stated that REBOA increases mortality compared with standard care alone in trauma patients with exsanguinating hemorrhage. Further studies and adequate simulation training programs in REBOA are critical to its successful implementation within a trauma system and to identify the optimum settings and patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Background: Death due to hemorrhagic shock, particularly, noncompressible truncal hemorrhage, remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently, whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer. In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared with pREBOA due to more oscillatory flow. Methods: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 min of automated pREBOA, iREBOA, or no balloon support (control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., eight key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 min). Citrated kaolin heparinase assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between the iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R time: P < 0.001; K time: P < 0.001) and clot strength (MA: P = 0.01; G: P = 0.02) over the duration of the experiment. Conclusions: Despite observing acute differences in peak proximal pressures between the iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA., Competing Interests: L.P.N. and T.K.W. are cofounders and shareholders of Certus Critical Care, Inc. NTPP served as a consultant for Certus Critical Care, Inc. The other authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Objective: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock., Background: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury., Methods: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality., Results: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups., Conclusions and Relevance: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences., Trial Registration: ClinicalTrials.gov identifier: NCT04667468., Competing Interests: J.L.S. reports grants from the DoD; F.X.G. reports grants from the DoD; S.R.W. reports grants from the DoD; L.Z.K. reports grants and consulting fees from University of Maryland/BARDA, personal fees from Gamma Diagnostics, Coagulant Therapeutics, Haemonetics, other from Cerus, outside the submitted work; A.E.K. reports being founder of CaptureDx; J.C. reports participates on the steering committee for Faraday Pharmaceuticals; M.D.N. has received grants from National Institutes of Health, Department of Defense, DARPA, Haemonetics, Alexion and Instrumentation Laboratories, honoraria for lectures from Haemonetics and Takeda, support for attending meetings and/or travel from Takeda; participates on a Data Safety Monitoring Board or Advisory Board from NHLBI CONNECTS Steering Committee; is the Chief Medical Officer, Haima Therapeutics, and has Patents planned, issued or pending (US Patent 11,408.844; US Patent 9.072,760), outside the submitted work; P.C.S. reports personal fees from Hemanext, Cerus, participates in advisory board for Octapharma,and Haima, and is the Co-Founder and Chief Medical Officer of Kalocyte, outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Globally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time-sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR - correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non-coagulopathic resuscitant has profound potential for application in trauma medicine., (© 2024 Wiley-VCH GmbH.)

Background: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer's (AR) and Lactate Ringer's solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear., Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury., Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats' survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity., Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Tan et al.)

Background: Fiberoptic-guided intubation is considered as "gold standard" of difficult airway management. Management of the airway in prone position in patients with severe trauma presenting with penetrating waist and hip injury poses a major challenge to the anesthesiologist., Case Presentation: A man presented with severe multiple trauma and hemorrhagic shock as a result of an industrial accident with several deformed steel bars penetrating the left lower waist and hip. It was decided to schedule an exploratory laparotomy following extracting the deformed steel bars. Successful administration of awake fiberoptic nasotracheal intubation, performed in a prone position under airway blocks and appropriate sedation, allowed for the procedure. The exploratory laparotomy revealed damage to multiple organs, which were repaired sequentially during a 7-hour surgical operation. The patient's recovery was uneventful, and he was discharged from the hospital one month after the surgery., Conclusions: Awake fiberoptic nasotracheal intubation, along with airway blocks and appropriate sedation, can be a viable option in patients with severe multiple trauma in the prone position., (© 2024. The Author(s).)

Background: Although whole blood (WB) transfusion was reported to improve survival in trauma patients with hemorrhagic shock, little is known whether a higher proportion of WB is associated with an improved survival. This study aimed to evaluate the association between whole blood ratio (WBR) and the risk of mortality in trauma patients requiring massive blood transfusion., Methods: We performed a retrospective cohort study from the ACS-TQIP between 2020 and 2021. Patients were aged ≥ 18 years and received WB within 4 h of hospital arrival as a part of massive blood transfusion. Study patients were categorized into four groups based on the quartiles of WBR. Primary outcome was 24-h mortality and secondary outcome was 30-day mortality. Multivariable logistic regression analysis, fitted with generalized estimating equations, was performed to adjust for confounding factors and accounted for within-hospital clustering., Results: A total of 4087 patients were eligible for analysis. The median age was 37 years (interquartile range [IQR]: 27-53 years), and 85.0% of patients were male. The median number of WB transfusions was 2.3 units (IQR 2.0-4.0 units), and the total transfusion volume was 4940 ml (IQR 3350-8504). When compared to the lowest WBR quartile, the highest WBR quartile had lower adjusted 24-h mortality (adjusted odds ratio [AOR]: 0.61, 95% confidence interval [CI]: 0.46-0.81) and 30-day mortality (AOR 0.58; 95% CI 0.45-0.75)., Conclusion: The probability of mortality consistently decreased with higher WBR in trauma patients requiring massive blood transfusion., (© 2024. The Author(s).)

Introduction: Whole blood (WB) has recently gained increased popularity as an adjunct to the resuscitation of hemorrhaging civilian trauma patients. We aimed to assess the nationwide outcomes of using WB as an adjunct to component therapy (CT) versus CT alone in resuscitating geriatric trauma patients., Methods: We performed a 5-y (2017-2021) retrospective analysis of the Trauma Quality Improvement Program. We included geriatric (age, ≥65 y) trauma patients presenting with hemorrhagic shock (shock index >1) and requiring at least 4 units of packed red blood cells in 4 h. Patients with severe head injuries (head Abbreviated Injury Scale ≥3) and transferred patients were excluded. Patients were stratified into WB-CT versus CT only. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications. Multivariable regression analysis was performed, adjusting for potential confounding factors., Results: A total of 1194 patients were identified, of which 141 (12%) received WB. The mean ± standard deviation age was 74 ± 7 y, 67.5% were male, and 83.4% had penetrating injuries. The median [interquartile range] Injury Severity Score was 19 [13-29], with no difference among study groups (P = 0.059). Overall, 6-h, 24-h, and in-hospital mortality were 16%, 23.1%, and 43.6%, respectively. On multivariable regression analysis, WB was independently associated with reduced 24-h (odds ratio, 0.62 [0.41-0.94]; P = 0.024), and in-hospital mortality (odds ratio, 0.60 [0.40-0.90]; P = 0.013), but not with major complications (odds ratio, 0.78 [0.53-1.15]; P = 0.207)., Conclusions: Transfusion of WB as an adjunct to CT is associated with improved early and overall mortality in geriatric trauma patients presenting with severe hemorrhage. The findings from this study are clinically important, as this is an essential first step in prioritizing the selection of WB resuscitation for geriatric trauma patients presenting with hemorrhagic shock., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hemorrhagic shock results in acute respiratory failure due to respiratory muscle fatigue and inadequate pulmonary blood flow. Because positive pressure ventilation can reduce venous return and cardiac output, clinicians should use the minimum possible mean airway pressure during assisted or mechanical ventilation, particularly during episodes of severe hypovolemia. Hypoperfusion also worsens dead space fraction. Therefore, clinicians should monitor capnography during mechanical ventilation and recognize that hypercapnia may be treated with fluid resuscitation rather than increasing minute ventilation.

Haemorrhagic shock, which arises as a complication of pelvic fracture subsequent to severe trauma, represents a perilous state. The utilization of interventional endovascular haemostasis assumes a pivotal role in the management of patients with vascular injury following pelvic fracture. This article reports the treatment of a patient with pelvic fracture caused by a serious work-related vehicle accident. Despite the implementation of timely blood and fluid transfusion to combat shock, the application of aortic balloon obstruction, and interventional iliac artery embolization for haemostasis, the patient's condition failed to display any discernible improvement. Repeat angiography further revealed a displacement of the interventional embolization material, and the patient subsequently died of multiple organ failure. The occurrence of spring coil displacement is infrequent, but the consequences thereof are considered grave, necessitating meticulous discernment in the selection of haemostatic materials for this type of patient. The diagnostic and therapeutic processes encompassing the particular case described here were analysed and are discussed with the objective of augmenting the efficacy and success rate of treatment modalities for patients in similar circumstances., Competing Interests: Declaration of conflicting interestAll Authors declare that there is no conflict of interest.

Introduction: Whole blood resuscitation for hemorrhagic shock in trauma represents an opportunity to correct coagulopathy in trauma while also supplying red blood cells. The production of microvesicles in stored whole blood and their effect on its hemostatic parameters have not been described in previous literature. We hypothesized that microvesicles in aged stored whole blood are procoagulant and increase thrombin production via phosphatidylserine., Methods: Whole blood was obtained from male C57BL/6 male mice and stored in anticoagulant solution for up to 10 days. At intervals, stored whole blood underwent examination with rotational thromboelastography, and platelet-poor plasma was prepared for analysis of thrombin generation. Microvesicles were prepared from 10-day-old whole blood aliquots and added to fresh whole blood or platelet-poor plasma to assess changes in coagulation and thrombin generation. Microvesicles were treated with recombinant mouse lactadherin prior to addition to plasma to inhibit phosphatidylserine's role in thrombin generation., Results: Aged murine whole blood had decreased fibrin clot formation compared with fresh samples with decreased plasma fibrinogen levels. Thrombin generation in plasma from aged blood increased over time of storage. The addition of microvesicles to fresh plasma resulted in increased thrombin generation compared with controls. When phosphatidylserine on microvesicles was blocked with lactadherin, there was no difference in the endogenous thrombin potential, but the generation of thrombin was blunted with lower peak thrombin levels., Conclusion: Cold storage of murine whole blood results in decreased fibrinogen levels and fibrin clot formation. Aged whole blood demonstrates increased thrombin generation, and this is due in part to microvesicle production in stored whole blood. One mechanism by which microvesicles are procoagulant is by phosphatidylserine expression on their membranes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Hemorrhagic shock is a major source of morbidity and mortality worldwide. While whole blood or blood product transfusion is a first-line treatment, maintaining robust supplies presents significant logistical challenges, particularly in austere environments. OMX is a novel nonhemoglobin (Hb)-based oxygen carrier derived from the H-NOX (heme-nitric oxide/oxygen binding) protein family. Because of their engineered oxygen (O 2 ) affinities, OMX proteins only deliver O 2 to severely hypoxic tissues. Additionally, unlike Hb-based oxygen carriers, OMX proteins do not scavenge nitric oxide in the vasculature. To determine the safety and efficacy of OMX in supporting tissue oxygen delivery and cardiovascular function in a large animal model of controlled hemorrhage, 2-3-week-old lambs were anesthetized, intubated, and mechanically ventilated. Hypovolemic shock was induced by acute hemorrhage to obtain a 50% reduction over 30 min. Vehicle (n = 16) or 400 mg/kg OMX (n = 13) treatment was administered over 15 min. Hemodynamics, arterial blood gases, and laboratory values were monitored throughout the 6-h study. Comparisons between groups were made using t tests, Wilcoxon rank sum test, and Fisher's exact test. Survival was assessed using Kaplan-Meier curves and the log-rank test. We found that OMX was well-tolerated and significantly improved lactate and base deficit trends, and hemodynamic indices ( P < 0.05). Median survival time was greater in the OMX-treated group (4.7 vs. 6.0 h, P < 0.003), and overall survival was significantly increased in the OMX-treated group (25% vs. 85%, P = 0.004). We conclude that OMX is well-tolerated and improves metabolic, hemodynamic, and survival outcomes in an ovine model of controlled hemorrhagic shock., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Objective: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is designed to manage severe hemorrhagic shock. Popularized in medical care during military conflicts, the concept has emerged as a lifesaving technique that is utilized around the United States. Literature on risks of REBOA placement, especially vascular injuries, are not well-reported. Our goal was to assess the incidence of vascular injury from REBOA placement and the risk factors associated with injury and death among these patients at our institution., Methods: We performed a retrospective cohort study of all patients who underwent REBOA placement between September 2017 and June 2022 at our Level 1 Trauma Center. The primary outcome variable was the presence of an injury related to REBOA insertion or use. Secondary outcomes studied were limb loss, the need for dialysis, and mortality. Data were analyzed using descriptive statistics, χ 2 , and t-tests as appropriate for the variable type., Results: We identified 99 patients who underwent REBOA placement during the study period. The mean age of patients was 43.1 ± 17.2 years, and 67.7% (67/99) were males. The majority of injuries were from blunt trauma (79.8%; 79/99). Twelve of the patients (12.1%; 12/99) had a vascular injury related to REBOA placement. All but one required intervention. The complications included local vessel injury (58.3%; 7/12), distal embolization (16.7%; 2/12), excessive bleeding requiring vascular consult (8.3%; 1/12), pseudoaneurysm requiring intervention (8.3%; 1/12), and one incident of inability to remove the REBOA device (8.3%; 1/12). The repairs were performed by vascular surgery (75%; 9/12), interventional radiology (16.7%; 2/12), and trauma surgery (8.3%; 1/12). There was no association of age, gender, race, and blunt vs penetrating injury to REBOA-related complications. Mortality in this patient population was high (40.4%), but there was no association with REBOA-related complications. Ipsilateral limb loss occurred in two patients with REBOA-related injuries, but both were due to their injuries and not to REBOA-related ischemia., Conclusions: Although vascular complications are not unusual in REBOA placement, there does not appear to be an association with limb loss, dialysis, or mortality if they are addressed promptly. Close coordination between vascular surgeons and trauma surgeons is essential in patients undergoing REBOA placement., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. All rights reserved.)

Background: The purpose of the study was to evaluate the mortality of patients who received Resuscitative Endovascular Balloon Occlusion of The Aorta (REBOA) in severe pelvic fracture with hemorrhagic shock., Methods: The American College of Surgeon Trauma Quality Improvement Program (ACS-TQIP) database for the calendar years 2017-2019 was accessed for the study. The study included all patients aged 15 years and older who sustained severe pelvic fractures, defined as an injury with an abbreviated injury scale (AIS) score of ≥ 3, and who presented with the lowest systolic blood pressure (SBP) of < 90 mmHg. Patients with severe brain injury were excluded from the study. Propensity score matching was used to compare the patients who received REBOA with similar characteristics to patients who did not receive REBOA., Results: Out of 3,186 patients who qualified for the study, 35(1.1%) patients received REBOA for an ongoing hemorrhagic shock with severe pelvic fracture. The propensity matching created 35 pairs of patients. The pair-matched analysis showed no significant differences between the group who received REBOA and the group that did not receive REBOA regarding patients' demography, injury severity, severity of pelvic fractures, lowest blood pressure at initial assessment and laparotomies. There was no significant difference found between REBOA versus no REBOA group in overall in-hospital mortality (34.3% vs. 28.6, P = 0.789)., Conclusion: Our study did not identify any mortality advantage in patients who received REBOA in hemorrhagic shock associated with severe pelvic fracture compared to a similar cohort of patients who did not receive REBOA. A larger sample size prospective study is needed to validate our results., Case-Control Retrospective Study: Level of Evidence IV., (© 2024. The Author(s).)

The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute  Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer-Lemeshow test (χ 2  = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma., (© 2024. The Author(s).)

The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging. Since microcirculation and mitochondrial respiration are main components of the terminal stretch of tissue oxygenation, the evaluation of microcirculatory and mitochondrial variables could identify tissues at risk during hypoxic challenges, indicate an increase of intestinal injury, and improve our understanding of regional pathophysiology during acute hemorrhage. Furthermore, improving intestinal microcirculation or mitochondrial respiration, e.g. by remote ischemic preconditioning (RIPC) that was reported to exert a sufficient tissue protection in various tissues and was linked to mediators with vasoactive properties could maintain intestinal integrity. In this study, postcapillary oxygen saturation (µHbO 2 ), microvascular flow index (MFI) and plasmatic D-lactate concentration revealed to be early markers of intestinal injury in a rodent model of experimental hemorrhagic shock. Mitochondrial function was not impaired in this experimental model of acute hemorrhage. Remote ischemic preconditioning (RIPC) failed to improve intestinal microcirculation and intestinal damage during hemorrhagic shock., (© 2024. The Author(s).)

Purpose of Review: Transfusion therapy commonly supports patient care during life-threatening injury and critical illness. Herein we examine the recent resurgence of whole blood (WB) resuscitation for patients in hemorrhagic shock following trauma and other causes of severe bleeding., Recent Findings: A growing body of literature supports the use of various forms of WB for hemostatic resuscitation in military and civilian trauma practice. Different types of WB include warm fresh whole blood (FWB) principally used in the military and low titer O cold stored whole blood (LTOWB) used in a variety of military and civilian settings. Incorporating WB initial resuscitation alongside subsequent component therapy reduces aggregate blood product utilization and improves early mortality without adversely impacting intensive care unit length of stay or infection rate. Applications outside the trauma bay include prehospital WB and use in patients with nontraumatic hemorrhagic shock., Summary: Whole blood may be transfused as FWB or LTOWB to support a hemostatic approach to hemorrhagic shock management. Although the bulk of WB resuscitation literature has appropriately focused on hemorrhagic shock following injury, extension to other etiologies of severe hemorrhage will benefit from focused inquiry to address cost, efficacy, approach, and patient-centered outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Combat casualty care can be complicated by transport times exceeding the "golden hour," with intervention and resuscitation limited to what the medic can carry. Pharmaceutical albumin comes highly saturated with nonesterified fatty acids (NEFAs). We recently showed that treatment with 25% bovine serum albumin (BSA) loaded with oleic acid, but not NEFA-free BSA, improved survival for hours after severe hemorrhage and often eliminated the need for resuscitation in rats. However, it was unknown whether pharmaceutical albumin, derived from human sources and loaded with caprylic acid (CA), would have the same benefits. We compared adjunct treatment with oleic acid-saturated BSA, CA-saturated BSA, pharmaceutical human serum albumin, or a no-albumin control in a similar rat hemorrhagic shock model to determine whether the three NEFA-albumin groups provided the same benefits relative to control. We found almost no significant differences among the NEFA-albumin groups in any measure. Mortality in controls was too low to allow for detection of improvement in survival, but NEFA-albumin groups had significantly improved hemodynamics, lactate clearance, and greatly reduced fluid requirements compared with controls. Contrary to expectations of "dehydration," 25% albumins shifted little additional fluid into the vasculature. Rather, they restored protein to the autotransfusion fluid. Nonesterified fatty acids-albumin did not worsen lung permeability, but we observed a loss of circulating protein suggesting it may have increased overall vascular permeability. Our findings suggest that, though imperfect, 25% human serum albumin could be a solution for resuscitation in austere conditions requiring prolonged field care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)