Treatment Of Hemorrhagic Shock Research Articles

Low-Titer O-Positive Whole Blood: Lessons From the Battlefield for Civilian Rural Hospitals.

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.

Apoptotic Cell-Based Therapy for the Modification of the Inflammatory Response to Hemorrhagic Shock.

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. 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. 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. 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.

Hemostatic Evaluation of Refrigerated Whole Blood Stored 7 Days Post-Expiration.

The United States Army has shifted doctrine to focus on large-scale combat operations against peer to near-peer adversaries. Future conflicts could result in a limited supply chain, leaving medical providers with only expired blood products for treatment of hemorrhagic shock. This study evaluated quality, function, and safety metrics of whole blood stored for 1 week past regulated expiration (i.e., 35 days, in CPDA-1). Whole blood units (n = 6) were collected in citrate phosphate dextrose adenine-1 (CPDA-1) anticoagulant and stored refrigerated for up to 42 days. Units were sampled on days 35, 37, 39, and 42 of storage and evaluated for the following: complete blood count, blood metabolism and chemistries, clotting dynamics, and presence of bacteria. The majority of evaluated parameters fell outside of normal clinical ranges beginning at day 35 of storage. At 42 days, blood pH was 6.58 ± 0.038, hemolysis was significantly increased (P = .037 vs day 35), and bacterial contamination was not evident. Glucose levels continuously dropped during extended storage. K+ was significantly increased at day 42 compared to day 35 (P = .010). A significant reduction in clot strength, factor V activity, and factor VIII activity was evident beginning at day 39 of storage. Storage of whole blood out to 42 days results in a continuous decline in function, but further in vivo safety studies should be performed to determine if the benefits of expired blood outweigh the risks. Other methods to safely extend storage of whole blood that maintain hemostatic function and preserve safety should be investigated, with emphasis placed on methods that reduce potassium leak and/or hemolysis.

Receipt of RhD-positive whole blood for life-threatening bleeding in female children: A survey in alloimmunized mothers regarding minimum acceptable survival benefit relative to risk of maternal alloimmunization to anti-D.

Low-titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD-positive units due to short supply of RhD-negative LTOWB. Practitioners must choose between using RhD-positive LTOWB when RhD-negative is unavailable against the risk to a female of childbearing potential of becoming RhD-alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD-negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD-positive blood for an injured RhD negative female child. A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy. Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD-positive transfusions for a female child was 4% (1%-14%). This was not different between females with and without a history of severe or fatal HDFN (p = .08 and 0.38, respectively). Alloimmunized mothers would accept the risk of D-alloimmunization in a RhD-negative female child for improved survival in cases of life-threatening bleeding.

Prehospital Extended FAST Exams Improve Clinical Decision Making by Helicopter EMS Crews: A Retrospective Case Series

Point of Care Ultrasound (POCUS) has seen increasing use in the prehospital environment over the last decade, primarily with the extended focused assessment with sonography in trauma (eFAST) exam. Previous studies have shown prehospital eFAST exams are feasible in the helicopter transport environment but have yet to demonstrate effects on clinical care. This retrospective case series identified 655 patients with blunt thoraco-abdominal trauma or concern for pneumothorax due to penetrating injury transported by a single helicopter EMS (HEMS) program over a two-year period after introducing POCUS. Of those patients, 258 received prehospital ultrasound which was reported to change clinical care in seven cases (2.7%, 95%-CI [1.1–5.5]). This was primarily through preventing unnecessary needle thoracostomy and initiating blood transfusion for treatment of hemorrhagic shock in cases where the degree of shock was unclear due to inconsistent vital signs. This study highlights the improvements in clinical care that may result from the introduction of eFAST exams in the prehospital environment.

Lilrb4 ameliorates ileal injury in rats with hemorrhagic shock and suppresses the activation of NF-κB signaling pathway

Hemorrhagic shock (HS) leads to intestinal damage and subsequent multiple organ dysfunction syndrome. Intestinal barrier dysfunction is the main cause of multiple organ failure associated with HS. Leukocyte immunoglobulin-like receptor B4 (Lilrb4) belongs to the Ig superfamily and is a vital natural immunomodulatory receptor. The purpose of this study was to identify the role and molecular mechanism of Lilrb4 in HS-induced ileal injury. In this work, HS was established by femoral artery cannula and 90 min of HS (blood pressure, 35–40 mmHg), followed by resuscitation. RNA sequencing analysis showed that Lilrb4 was highly expressed in the ileum of HS rats. As observed, HS rats exhibited severe ileal injury, characterized by enlarged subepithelial space, edema, exfoliation and extensive loss of villi. Whereas, lentivirus system-mediated Lilrb4 overexpression considerably mitigated these alterations. HS led to increased release of markers associated with intestinal injury, which was effectively reversed by Lilrb4 overexpression. In addition, after resuscitation, Lilrb4 overexpression inhibited HS-triggered inflammatory response, as evidenced by decreased levels of proinflammatory cytokines. Lilrb4 also inhibited the activation of NF-κB signal induced by HS. Notably, Lilrb4 modulated the balance of regulatory T (Treg)-T helper 17 (Th17) cells in the mesenteric lymph node (MLN), which may also contribute to its protective role in HS progression. In aggregate, these findings confirmed that Lilrb4 overexpression protected against ileal injury caused by HS, indicating that Lilrb4 may be a potential candidate for the treatment of HS.

Sodium bicarbonate Ringer's solution for hemorrhagic shock: A meta-analysis comparing crystalloid solutions

BackgroundThe choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics. ObjectiveTo evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions. MethodA comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events. ResultThe meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p = 0.08; I2 = 0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p < 0.0001; I2 = 22%), a mean difference in heart rate of −4.49 (95% CI: −7.55, −1.44; p = 0.004; I2 = 13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: −0.85, 5.47; p = 0.15; I2 = 66%). ConclusionBRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver.

Vascular injury during lumbar discectomy: risk factors, diagnosis, methods of surgical correction, features of anaesthetic management and intensive care

One of the priority tasks in neurosurgery is to reduce the frequency of postoperative complications and mortality. Lumbar discectomy is the most frequently performed intervention in spinal neurosurgery and it is a fairly safe procedure. One of the possible intraoperative surgical complications, that threatens the patient’s life is vascular injury. The first clinical case of damage to the large vessels during discectomy was described in 1945. It is believed that the frequency of this complication is 1‒5 cases per 10,000 surgical interventions, but the literature notes that these figures may be significantly underestimated. Some authors indicate that the frequency of this complication, despite the development of surgical techniques over the past 50 years, has not significantly decreased, so it is important for surgeons to be informed and alert about the possibility of such a problem. Among the factors that significantly increase the risk of vascular damage congenital, acquired and technical are determined. Variability of clinical symptoms of damage to lagre vessels is due to different localization of injury, type (arterial, venous or combined) and scale of vascular disaster. For each level of surgical intervention, the "most typical" vessel damage is identified. Vascular injury during discectomy can occur according to three clinical and pathomorphological scenarios: manifestation of vessel rupture symptoms, arteriovenous fistula or a pseudoaneurysm formation. According to different authors, the frequency of these findings varies significantly. This review examines the symptoms of possible variants of vascular damage development during discectomy and describes the characteristics of surgical correction methods. Along with clarifying the location and variant of vascular damage, the critical thing is assessing the amount of blood loss and the rate of ongoing bleeding. In the case of suspected massive bleeding, the paramount importance is the involvement of additional medical personnel for the surgical haemostasis and providing sufficient blood for haemotransfusions. In case of a vascular accident, the key requirement for adequate anaesthetic management is the maintenance of permissive arterial hypotension until the moment of surgical haemostasis. Targeted treatment of haemorrhagic shock in case of damage to large vessels consists of rapid haemostatic resuscitation including blood components and products in a balanced 1:1:1 ratio, such as plasma, red blood cells, fresh frozen plasma, platelets, and coagulation factors. In Ukraine, obtaining a sufficient amount of blood components and products (according to the protocol of massive haemotransfusion) in case of unpredicted blood loss is a difficult task, therefore, in the absence of certain components or blood products, whole blood can be used as an alternative. The number and severity of complications and outcomes primarily depend on the efficiency and timeliness of blood transfusions, along with the speed of surgical arrest of bleeding. This publication describes in detail the main points of management of patients with massive bleeding according to modern international standards and Ukraine regulatory documents.

Mesenchymal stem cells overexpressing PBX1 alleviates haemorrhagic shock-induced kidney damage by inhibiting NF-κB activation

Mesenchymal stem cells (MSCs) have favourable outcomes in the treatment of kidney diseases. Pre-B-cell leukaemia transcription factor 1 (PBX1) has been reported to be a regulator of self-renewal of stem cells. Whether PBX1 is beneficial to MSCs in the treatment of haemorrhagic shock (HS)-induced kidney damage is unknown. We overexpressed PBX1 in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human bone marrow-derived mesenchymal stem cells (hBMSCs) to treat rats with HS and hypoxia-treated human proximal tubule epithelial cells (HK-2), respectively. The results indicated that PBX1 enhanced the homing capacity of rBMSCs to kidney tissues and that treatment with rBMSCs overexpressing PBX1 improved the indicators of kidney function, alleviated structural damage to kidney tissues. Furthermore, administration with rBMSCs overexpressing PBX1 inhibited HS-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the release of proinflammatory cytokines, and further attenuated apoptosis. We then determined whether NF-κB, an important factor in NLRP3 activation and the regulation of inflammation, participates in HS-induced kidney damage, and we found that rBMSCs overexpressing PBX1 inhibited NF-κB activation by decreasing the p-IκBα/IκBα and p-p65/p65 ratios and inhibiting the nuclear translocation and decreasing the DNA-binding capacity of NF-κB. hBMSCs overexpressing PBX1 also exhibited protective effects on HK-2 cells exposed to hypoxia, as shown by the increase in cell viability, the mitigation of apoptosis, the decrease in inflammation, and the inhibition of NF-κB and NLRP3 inflammasome activation. Our study demonstrates that MSCs overexpressing PBX1 ameliorates HS-induced kidney damage by inhibiting NF-κB pathway-mediated NLRP3 inflammasome activation and the inflammatory response.

Comparative Analysis ofWhole Blood Infusion Effects: Assessing LifeFlow Versus Pressure Bag ina Sus scrofa Model.

To improve survival for hemorrhagic shock treatment, guidelines emphasize two patient care priorities: (1) immediate hemorrhage control and (2) early resuscitation with whole blood or blood products. The LifeFlow device is designed to rapidly infuse blood products. However, the effects of using this device compared to pressure-bag systems remain unclear. We hypothesize that there will be no laboratory-measured difference with the blood when infused through the LifeFlow versus the current standard pressure bag system. Two units of fresh whole blood were obtained from a sus scrofa model. One unit was "infused" using the LifeFlow with the other unit used as a control through a standard pressure bag system into an empty bag. The "before" measurements were obtained from blood samples from a standard fresh whole blood collection bag. The blood was "infused" into a whole blood bag devoid of storage solution from which the "after" measurements were obtained. This study utilized 22 clinically healthy sus scrofa. Blood units were primarily obtained from a left subclavian central line (50.0%). The median time to acquire and administer a unit of blood was similar for both the LifeFlow device (8.4 min and 8.1 min) and the pressure bag (8.7 min and 7.4 min). No significant differences were found in the total time to acquire or administer blood between the two devices. The median volume of blood acquired was 500 mL for both groups. While no significant differences in blood parameters were observed between the two devices, significant differences were noted when comparing pre- and post-transfusion values within each device. For the LifeFlow device, an increase in hemoglobin and chloride levels and a decrease in thromboplastin time and glucose levels were observed. With the pressure bag, only a decrease in blood urea nitrogen was observed. In comparing the LifeFlow to the pressure bag, there were no significant differences noted in the total time to acquire or administer a whole unit of blood. However, there were differences with several laboratory parameters of unclear clinical significance.

The artificial oxygen carrier erythrocruorin-characteristics and potential significance in medicine.

The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell (RBC) substitutes. HBOCs are versatile agents that can be used in the treatment of hemorrhagic shock. However, many of the RBC substitutes that are based on mammalian hemoglobins have presented key limitations such as instability and toxicity. In contrast, erythrocruorins (Ecs) are other types of HBOCs that may not suffer these disadvantages. Ecs are giant metalloproteins found in annelids, crustaceans, and some other invertebrates. Thus far, the Ecs of Lumbricus terrestris (LtEc) and Arenicola marina (AmEc) are the most thoroughly studied. Based on data from preclinical transfusion studies, it was found that these compounds not only efficiently transport oxygen and have anti-inflammatory properties, but also can be modified to further increase their effectiveness. This literature review focuses on the structure, properties, and application of Ecs, as well as their advantages over other HBOCs. Development of methods for both the stabilization and purification of erythrocruorin could confer to enhanced access to artificial blood resources.

Acute (profuse) hemorrhoidal bleeding

Objective. Hemorrhoids is one of the most common diseases in adult coloproctological practice, the main manifestation of which is bleeding of different degree of activity and complexity. The aim of the study was to analyze the results of diagnostics and treatment of patients with different stages of hemorrhoids for 3 years. Materials and methods. The results of diagnostics and treatment of patients with different stages of hemorrhoids treated in the coloproctological unit for 3 years (20192021) were analyzed. Results. The article considers the hemorrhoidal bleeding and the possibility of classification to optimize treatment; an algorithm used for rendering medical care to this group of patients is presented. The case histories of patients with hemorrhoids, treated at the First Republican Clinical Hospital of Udmurt Republic, were analyzed. Conclusions. Patients with profuse hemorrhoidal bleeding need hospitalization to the resuscitation unit, immediate identification and treatment of hemorrhagic shock. The offered protocol (algorithm) of managing patients permitted to work in a team, improve the quality of rendering medical care to patients with profuse hemorrhoidal bleeding and avoid lethal outcomes.

Cryptotanshinone ameliorates hemorrhagic shock-induced liver injury via activating the Nrf2 signaling pathway.

Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activitywere suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.

Impairment of Mesenteric Perfusion as a Marker of Major Bleeding in Trauma Patients.

The majority of potentially preventable mortality in trauma patients is related to bleeding; therefore, early recognition and effective treatment of hemorrhagic shock impose a cardinal challenge for trauma teams worldwide. The reduction in mesenteric perfusion (MP) is among the first compensatory responses to blood loss; however, there is no adequate tool for splanchnic hemodynamic monitoring in emergency patient care. In this narrative review, (i) methods based on flowmetry, CT imaging, video microscopy (VM), measurement of laboratory markers, spectroscopy, and tissue capnometry were critically analyzed with respect to their accessibility, and applicability, sensitivity, and specificity. (ii) Then, we demonstrated that derangement of MP is a promising diagnostic indicator of blood loss. (iii) Finally, we discussed a new diagnostic method for the evaluation of hemorrhage based on exhaled methane (CH4) measurement. Conclusions: Monitoring the MP is a feasible option for the evaluation of blood loss. There are a wide range of experimentally used methodologies; however, due to their practical limitations, only a fraction of them could be integrated into routine emergency trauma care. According to our comprehensive review, breath analysis, including exhaled CH4 measurement, would provide the possibility for continuous, non-invasive monitoring of blood loss.

Evaluation of hemorrhagic shock and traumatic brain injury effects on hemodynamics and metabolomics

Traumatic brain injury (TBI) is often accompanied by hemorrhage. However, treatment of hemorrhagic shock (HS) after TBI is challenging because the treatment strategies for TBI and HS often conflict. Little is known about the complex pathophysiological differences between these two traumas when happening individually or combined. The aim of the present study was to evaluate effects of HS and TBI individually and combined on hemodynamics, baroreflex and brain metabolomics. Male Wistar rats were instrumented with catheters and subjected to TBI through a pneumatic controlled cortical impact. HS was induced by blood withdrawal to achieve a blood pressure (BP) between 35-40mmHg, and this hypotensive state was maintained for 90 min. Animals were separated into 4 groups (n=5): Sham (underwent surgery, but no TBI or HS was done), HS (animals were placed in the stereotaxic, but no TBI), TBI (TBI was performed and timeline was followed as described, but no HS was done), and TBI+HS. Rats were sacrificed 90 min after HS and tissues were harvested. BP, heart rate (HR), and indices of spontaneous baroreflex sensitivity were evaluated at baseline, 10 min after TBI, and at 10 and 90 min after HS. The brain was harvested and a metabolomic analysis for tricarboxylic acid (TCA) cycle, amino acids and lipids was performed in the impacted area. BP decreased in the TBI group compared to Sham and, as expected, it severely decreased in HS and TBI+HS groups, once they were kept at lower pressure levels for 90 min. Heart Rate (HR) was lower in the HS group compared to Sham and TBI groups. It was observed that HS decreases the BP alteration events’ number during a fixed 10 min period compared to Sham and TBI groups, however the association of TBI with HS normalized this parameter. This suggests that HS is decreasing BP variability in the HS group, while the association of HS with TBI did not show the same response. Baroreflex sensitivity was higher in both HS and HS+TBI compared to both Sham and TBI groups. TCA cycle and amino acids metabolites increased in all the groups with trauma compared to Sham, however the increase in the HS and TBI+HS was around 2.5X-fold, while for the TBI group it was around 1.5X-fold. Moreover, the lipids metabolites decreased for all the groups submitted to trauma, with the highest effects observed for the groups submitted to HS and TBI+HS. These results suggest that HS has a higher effect on metabolites abnormalities compared to TBI alone. Our results suggest that HS has a higher contribution for hemodynamics and metabolism abnormalities when compared to TBI alone. It is interesting that the association of TBI with HS does not seem to change parameters such HR and BP variability. However, further investigations are necessary to better understand the impact of the lack of alteration of these hemodynamics parameters, since this trauma combination is complex and the adequate treatment for these situations remains unclear. This study was supported by National Institutes of Health grants R01HL162120, R01HL159862 and the Department of Defense under grants W81XWH1810059. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cold storage of whole blood in an additive solution containing apoptotic and necrotic inhibitors.

Whole blood (WB) reigns superior to component therapy for the treatment of hemorrhagic shock on the battlefield. Though cold storage of WB offers a shelf life of 21 to 35 days, storage lesions and the potential for blood wastage remain. Storing WB in an additive solution (AS) containing apoptotic inhibitors may help preserve blood cell viability and improve blood quality over extended cold storage. Non-leukoreduced WB was obtained from healthy individuals and dosed with: AS, AS+Necrostatin-1 (AS+N1), AS+Boc-D-fmk (AS+B; apoptosis inhibitor), AS+Q-VD-OPh (AS+Q; apoptosis inhibitor), and Control (0.9% saline). Blood bags were kept refrigerated (1°-6°C) for 21 days. Bags were tested on days 0, 7, 14, and 21 for complete blood count, metabolism, clot formation, aggregation function, platelet activation, and red blood cell quality. Platelet count was better preserved in all AS-containing samples. All groups displayed increased glucose consumption and lactate production with storage. Furthermore, all groups displayed a similar decline in clot strength (max amplitude) over the 21-day storage period. Bags that received AS displayed greater preservation of GPIIb expression and lower phosphatidylserine exposure. P-selectin expression was increased in all AS groups. Treatment of hemorrhagic shock with WB transfusion is logistically simpler than component therapy. Results from our study suggest that refrigerated WB stored with an AS containing apoptotic and necrotic inhibitors helps better preserve platelet count but does not improve platelet function. The future development of WB ASs is warranted to optimize both platelet quality and hemostatic function.

Effects of Mdivi-1 on Extending the Golden Treatment Time following Hemorrhagic Shock in Hot Environment in Rats.

It is found that a hot environment aggravates hemorrhagic shock-induced internal environment and organ dysfunction. Meanwhile mitochondria show over-fission. Whether inhibition of mitochondrial fission benefits from the early treatment of hemorrhagic shock under a hot environment is unclear. An uncontrolled hemorrhagic shock model in rats is used, and the effects of mitochondrial fission inhibitor mdivi-1 on mitochondrial function, organ function, and survival rate of rats are measured. The results show that 0.1-3 mg/kg mdivi-1 antagonizes hemorrhagic shock-induced mitochondrial fragment. In addition, mdivi-1 improves mitochondrial function, and alleviates hemorrhagic shock-induced oxidative stress and inflammation under a hot environment. Further studies show that 0.1-3 mg/kg Mdivi-1 reduces blood loss, and maintains a mean artery pressure (MAP) of 50-60 mmHg before bleeding-stops after hemorrhagic shock, compared with single Lactate Ringer's (LR) resuscitation. Notably, 1 mg/kg of Mdivi-1 extends the time of hypotensive resuscitation to 2-3 h. During 1 or 2 h of ligation, Mdivi-1 prolongs survival time and protects vital organ function by rescuing mitochondrial morphology and improving mitochondrial function. These results suggest Mdivi-1 is suitable for the early treatment of hemorrhagic shock under a hot environment and can extend the golden treatment time to 2-3 hour for hemorrhagic shock under a hot environment.

A narrative review of prehospital hemorrhagic shock treatment with non-blood product medications.

Hemorrhagic shock remains a leading cause of death in both military and civilian trauma casualties. While standard of care involves blood product administration, maintaining normothermia, and restoring hemostatic function, alternative strategies to treat severe hemorrhage at or near the point of injury are needed. We reviewed adjunct solutions for managing severe hemorrhage in the prehospital environment. We performed a literature review by searching PubMed with a combination of several keywords. Additional pertinent studies were identified by crossreferencing primary articles. Clinical experience of each author was also considered. We identified several promising antishock therapies that can be utilized in the prehospital setting: ethinyl estradiol sulfate (EES), polyethylene glycol 20,000 (PEG20K), C1 esterase inhibitors (e.g. Berinert, Cinryze), cyclosporin A, niacin, bortezomib, rosiglitazone, icatibant, diazoxide, and valproic acid (VPA). Several studies show promising adjunct treatment options in the management of severe prehospital hemorrhage. While some are rarely used, many others are readily available and commonly utilized for other indications. This suggests the potential for future use in resourcelimited settings. Human studies and case reports supporting their use are currently lacking.

Association Between Profound Shock Signs and Peripheral Intravenous Access Success Rates in Trauma Patients in the Prehospital Scenario: A Retrospective Study.

Hemorrhage is the leading cause of preventable death in trauma patients, and establishment of intravenous (IV) access is essential for volume resuscitation, a key component in the treatment of hemorrhagic shock. IV access among patients in shock is generally considered more challenging, although data to support this notion are lacking. In this retrospective registry-based study, data were collected from the Israeli Defense Forces Trauma Registry (IDF-TR) regarding all prehospital trauma patients treated by IDF medical forces between January 2020 and April 2022, for whom IV access was attempted. Patients younger than 16 years, nonurgent patients, and patients with no detectable heart rate or blood pressure were excluded. Profound shock was defined as a heart rate >130 or a systolic blood pressure <90 mm Hg, and comparisons were made between patients with profound shock and those not exhibiting such signs. The primary outcome was the number of attempts required for first IV access success, which was regarded as an ordinal categorical variable: 1, 2, 3 and higher and ultimate failure. A multivariable ordinal logistic regression was performed to adjust for potential confounders. Patients' sex, age, mechanism of injury and best consciousness level, as well as type of event (military/nonmilitary), and the presence of multiple patients were included in the ordinal logistic regression multivariable analysis model based on previous publications. Five hundred thirty-seven patients were included, 15.7% of whom were recorded as having signs of profound shock. Peripheral IV access establishment first attempt success rates were higher in the nonshock group, and there was a lower rate of unsuccessful attempts in this group (80.8% vs 67.8% for the first attempt, 9.4% vs 16.7% for the second attempt, 3.8% vs 5.6% for the third and further attempts, and 6% vs 10% unsuccessful attempts, P = .04). In the univariable analysis, profound shock was associated with requirement for an increased number of IV attempts (odds ratio [OR], 1.94; confidence interval [CI], 1.17-3.15). The ordinal logistic regression multivariable analysis demonstrated that profound shock was associated with worse results regarding primary outcome (adjusted odds ratio [AOR], 1.84; CI, 1.07-3.10). The presence of profound shock in trauma patients in the prehospital scenario is associated with an increased number of attempts required for IV access establishment.

Infusion therapy as an important element of anesthetic strategy for the wounded with hemorrhagic shock

Hemorrhagic shock remains the main cause of death of the wounded in all wars and military conflicts. A key aspect in modern anesthetic strategy for the wounded with hemorrhagic shock is the strategy of a balanced infusion therapy. It consists in restricting the infusion of crystalloids and colloids and the earliest possible transfusion of blood products to a wounded person with massive hemorrhage. Currently, the main option for blood transfusion both in civilian health care facilities and in medical facilities of the Armed Forces of Ukraine is the use of the so-called component blood transfusion therapy, i.e. transfusion of packed red blood cells and fresh-frozen plasma. This approach is absolutely justified for elective surgical and somatic patients, but has a number of significant disadvantages in the treatment of wounded with massive hemorrhage. In addition, blood transfusion in the conditions of hostilities, disasters and emergency situations has additional logistical (quick availability) and safety (risk of errors when combining blood groups) requirements for blood preparations. Therefore, the issue of alternative, relative to component therapy, variants of transfusion therapy in the treatment of hemorrhagic shock becomes especially relevant.