Traumatic Hemorrhagic Shock Research Articles

Effects of Alprostadil Combined with Edaravone on Inflammation, Oxidative Stress and Pulmonary Function in Patients with Traumatic Hemorrhagic Shock.

The study aimed to explore the roles of alprostadil combined with edaravone in inflammation, oxidative stress and Pulmonary function in patients with traumatic hemorrhagic shock (HS). 80 patients with traumatic HS treated in Feicheng Hospital Affiliated to Shandong First Medical University and Tai'an City Central Hospital from January 2018 to January 2022 were enrolled and divided into observation group (n=40) and control group (n=40) according to the randomized control method. Patients in the control group were given alprostadil alone (5 g alprostadil + 10 mL normal saline) in addition to conventional treatment, while those in the observation group received edaravone (30 mg edaravone + 250 mL normal saline) on the basis of treatment in the control group. The patients in both groups were treated via intravenous infusion once a day for 5 days. 24 hours (h) after resuscitation, venous blood were collected to detect serum biochemical indicators such as blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Enzyme-linked immunosorbent assay (ELISA) was conducted to determine serum inflammatory factors. Lung lavage fluid was collected to examine pulmonaryfunction indicators such as myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) activity and to observe the oxygenation index (OI). Blood pressure was measured at admission and 24 h after surgery. The observation group had significantly lowered serum BUN, AST and ALT (p<0.05), the content of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as well as oxidative stress indexes like superoxide dismutase (SOD) and malondialdehyde (MDA) (p<0.05) and pulmonary function indicators (p<0.05) but overtly increased content of SOD and OI. Furthermore, the blood pressure in the observation group dropped to 30 mmHg at admission and rose to the normal range. Alprostadil combined with edaravone effectively reduces inflammatory factors and improves oxidative stress and pulmonary function in patients with traumatic HS, whose efficacy is significantly better than that of alprostadil alone.

A 2A ADENOSINE RECEPTORS REGULATE MULTIPLE ORGAN FAILURE AFTER HEMORRHAGIC SHOCK IN MICE.

Trauma hemorrhagic shock (T/HS) is a clinical condition that causes multiple organ failure that needs rapid intervention. Restricted oxygen at the cellular level causes inflammation and subsequent cell death. Adenosine triphosphate is the universal intracellular energy currency and an important extracellular inflammatory signaling molecule. Adenosine, an endogenous nucleotide formed as a result of the breakdown of adenosine triphosphate, is also released during T/HS. Adenosine binds to four G protein-coupled receptors (A 1R , A 2a , A 2b , A 3R ) called adenosine receptors or P1 receptors. In the present study, we evaluated the effect of activation, inactivation, and genetic absence of A2aR (A2aR -/- mice) on T/HS-induced multiple organ failure. Wild-type mice were pretreated (30 min before shock induction) with an agonist or antagonist and then subjected to T/HS by withdrawing arterial blood and maintaining the blood pressure between 28 and 32 mm Hg. A2aR -/- mice were subjected to T/HS in the absence of pharmacologic treatment. Neutrophil sequestration was assessed by detecting myeloperoxidase, and Evans blue dye (EBD) method was used to analyze lung permeability. Blood and lung inflammatory cytokine levels were determined by sandwich enzyme-linked immunosorbent assay. The liver enzymes aspartate aminotransferase and alanine aminotransferase were determined spectrophotometrically from plasma. Activation of the apoptotic cascade was evaluated using a mouse apoptosis array. Our results demonstrate that the selective A2aR agonist CGS21680 decreases lung neutrophil sequestration, lung proinflammatory cytokines IL-6 and TNF-α, and bronchoalveolar lavage EBD. Pretreatment with the selective antagonist ZM241385 and genetic blockade in A2aR -/- mice increased neutrophil sequestration, proinflammatory cytokine levels, and bronchoalveolar lavage fluid EBD. The myeloperoxidase level in the lung was also increased in A2aR -/- mice. We observed that antiapoptotic markers decreased significantly with the absence of A2aR in the lung and spleen after T/HS. In conclusion, our data demonstrate that activation of A2aR regulates organ injury and apoptosis in the setting of T/HS.

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study.

Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 – 250 mmHg) or normoxemia (target PaO2 80 – 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.

Characteristics and Risk Factors of Myocardial Injury after Traumatic Hemorrhagic Shock.

Myocardial injury increases major adverse cardiovascular events and mortality in patients with traumatic hemorrhagic shock, but its prevalence and risk factors remain unclear. This study aimed to assess the prevalence and risk factors of myocardial injury after traumatic hemorrhagic shock. This was an observational, retrospective cohort study of patients with traumatic hemorrhagic shock at a tertiary university hospital from November 2012 to July 2021. Patient characteristics and clinical variables were recorded in 314 patients. The outcome was the occurrence of myocardial injury after traumatic hemorrhagic shock. Risk factors for myocardial injury were identified using logistic regression. The incidence of myocardial injury after the traumatic hemorrhagic shock was 42.4%, and 95.5% of myocardial injuries occurred within the first three days after trauma. In the multivariate analysis, the independent risk factors for myocardial injury after traumatic hemorrhagic shock included heart rate of >100 beats/min (OR [odds ratio], 3.33; 95% confidence interval [CI], 1.56–7.09; p = 0.002), hemoglobin level of <70 g/L (OR, 3.50; 95% CI, 1.15–10.60; p = 0.027), prothrombin time of >15 s (OR, 2.39; 95% CI, 1.12–5.10; p = 0.024), acute kidney injury (OR, 2.75; 95% CI, 1.27–5.93; p = 0.01), and a higher APACHE II score (OR, 1.08; 95% CI, 1.01–1.15; p = 0.018). The area under the receiver operating characteristic curve for the prediction of myocardial injury after a traumatic hemorrhagic shock was 0.67 (95% CI, 0.68–0.79) for a heart rate of >100 beats/min, 0.67 (95% CI, 0.61–0.73) for hemoglobin level of <70 g/L, 0.66 (95% CI, 0.60–0.73) for prothrombin time of >15 s, 0.70 (95% CI, 0.64–0.76) for acute kidney injury, and 0.78 (95% CI, 0.73–0.83) for APACHE II scores. The incidence rate of myocardial injury in traumatic hemorrhagic shock is high, and heart rates of >100 beats/min, hemoglobin levels of <70 g/L, prothrombin times of >15 s, AKI and higher APACHE II scores are independent risk factors for myocardial injury after traumatic hemorrhagic shock. These findings may help clinicians to identify myocardial injury after traumatic hemorrhagic shock early and initiate appropriate treatment.

A Novel Therapeutic Approach With Sodium Pyruvate on Vital Signs, Acid-Base, and Metabolic Disturbances in Rats With a Combined Blast and Hemorrhagic Shock.

BackgroundBlast injuries from improvised explosive devices (IEDs) are known to cause blast traumatic brain injuries (bTBIs), hemorrhagic shock (HS), organ damage, mitochondrial dysfunction, and subsequent free radical production. A pre-citric acid cycle reagent, pyruvate, is suggested to improve mitochondrial ATP production through the activation of the mitochondrial gatekeeper enzyme “pyruvate dehydrogenase complex (PDH).” Our study aimed to investigate the role of physiologic, metabolic, and mitochondrial effects of hypertonic sodium pyruvate resuscitation in rats with a combined blast and HS injury.MethodsA pre-clinical rat model of combined injury with repetitive 20 PSI blast exposure accompanied with HS and fluid resuscitation (sodium pyruvate as metabolic adjuvant or hypertonic saline as control), followed by transfusion of shed blood was used in this study. Control sham animals (instrumental and time-matched) received anesthesia and cannulation, but neither received any injury nor treatment. The mean arterial pressure and heart rate were recorded throughout the experiment by a computerized program. Blood collected at T0 (baseline), T60 (after HS), and T180 (end) was analyzed for blood chemistry and mitochondrial PDH enzyme activity.ResultsSodium pyruvate resuscitation significantly improved the mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), hemodynamic stability (Shock index), and autonomic response (Kerdo index) after the HS and/or blast injury. Compared with the baseline values, plasma lactate and lactate/pyruvate ratios were significantly increased. In contrast, base excess BE/() was low and the pH was also acidotic <7.3, indicating the sign of metabolic acidosis after blast and HS in all animal groups. Sodium pyruvate infusion significantly corrected these parameters at the end of the experiment. The PDH activity also improved after the sodium pyruvate infusion.ConclusionIn our rat model of a combined blast and HS injury, hypertonic sodium pyruvate resuscitation was significantly effective in hemodynamic stabilization by correcting the acid–base status and mitochondrial mechanisms via its pyruvate dehydrogenase enzyme.

Current perspectives of artificial oxygen carriers as red blood cell substitutes: a review of old to cutting-edge technologies using in vitro and in vivo assessments.

BackgroundSeveral circumstances such as accidents, surgery, traumatic hemorrhagic shock, and other causalities cause major blood loss. Allogenic blood transfusion can be resuscitative for such conditions; however, it has numerous ambivalent effects, including supply shortage, needs for more time, cost for blood grouping, the possibility of spreading an infection, and short shelf-life. Hypoxia or ischemia causes heart failure, neurological problems, and organ damage in many patients. To address this emergent medical need for resuscitation and to treat hypoxic conditions as well as to enhance oxygen transportation, researchers aspire to achieve a robust technology aimed to develop safe and feasible red blood cell substitutes for effective oxygen transport.Area coveredThis review article provides an overview of the formulation, storage, shelf-life, clinical application, side effects, and current perspectives of artificial oxygen carriers (AOCs) as red blood cell substitutes. Moreover, the pre-clinical (in vitro and in vivo) assessments for the evaluation of the efficacy and safety of oxygen transport through AOCs are key considerations in this study. With the most significant technologies, hemoglobin- and perfluorocarbon-based oxygen carriers as well as other modern technologies, such as synthetically produced porphyrin-based AOCs and oxygen-carrying micro/nanobubbles, have also been elucidated.Expert opinionBoth hemoglobin- and perfluorocarbon-based oxygen carriers are significant, despite having the latter acting as safeguards; they are cost-effective, facile formulations which penetrate small blood vessels and remove arterial blockages due to their nano-size. They also show better biocompatibility and longer half-life circulation than other similar technologies.

Induction of endothelial barrier dysfunction by serum factors in rats subjected to traumatic brain injury and hemorrhagic shock.

Traumatic brain injury (TBI) has been associated with the development of indirect acute respiratory distress syndrome (ARDS). However, the causative relationship between TBI and lung injury remains unclear. To explore potential mechanisms linking TBI with the development of ARDS, we characterized the effects of serum factors released following TBI and hemorrhagic shock (HS) in a rat model on the pulmonary endothelial cell (EC) barrier dysfunction, a key feature of ARDS. We found that serum samples from animals exposed to both controlled cortical impact (CCI) and HS, but not from sham‐operated rats induced significant barrier dysfunction in human pulmonary artery EC monolayers at 2 days post injury. Thrombin inhibitor and thrombin receptor antagonist attenuated the acute phase of the serum‐induced trans‐endothelial resistance (TER) decline caused by CCI‐HS serum, but not in later time points. However, both the early and late phases of CCI‐HS‐induced EC permeability were inhibited by heparin. The barrier disruptive effects of CCI‐HS serum were also prevented by serum preincubation with heparin‐sepharose. Pulmonary EC treated for 3 h with serum from CCI‐HS rats demonstrated a significant decline in expression of EC junctional protein, VE‐Cadherin, and disassembly of peripheral EC adherens junction complexes monitored by immunostaining with VE‐cadherin antibody. These results suggest that exposure to CCI‐HS causes early and late‐phase barrier disruptive effects in vascular endothelium. While thrombin‐PAR1 signaling has been identified as a mechanism of acute EC permeability increase by CCI‐HS serum, the factor(s) defining long‐term EC barrier disruption in CCI‐HS model remains to be determined.

Correlation between Coagulation Fibrinolysis Function and Outcomes during Hospitalization in Patients with Severe Traumatic Hemorrhagic Shock.

Objective To analyze the correlation between coagulation fibrinolysis function and outcomes during hospitalization in patients with severe traumatic hemorrhagic shock. Methods A retrospective collection was performed on the clinical data of 106 patients with severe traumatic shock admitted to the hospital between January 2020 and January 2022. According to the injury severity score (ISS), they were divided into the S1 group (ISS <25 points, n = 70) and the S2 group (ISS ≥25 points, n = 36). The prothrombin time (PT), fibrinogen (Fib), thrombin time (TT), and activated partial thromboplastin time (APTT) were detected by the coagulation assay. The aD-dimer (D-D) was detected by an enzyme-linked immunosorbent assay. Antithrombin activity (AT : A) and plasminogen activity (PLG : A) were detected by the chromogenic substrate method. The relationship between coagulation fibrinolysis indexes and injury severity was analyzed by Spearman's correlation analysis. The predictive value of coagulation fibrinolysis indexes for outcomes of patients with severe traumatic hemorrhagic shock was evaluated by receiver operating characteristic (ROC) curves. Results The levels of PT, APTT, D-D, TT, AT : A and PLG : A in the S2 group were higher than those in S1 group, while the Fib level was lower than that in the S1 group (P < 0.05). A Spearman's analysis showed that PT, APTT, TT, D-D, AT : A, and PLG : A were positively correlated with injury severity (P < 0.05), while Fib was negatively correlated with it (P < 0.05). Among the 106 patients, there were 89 survived cases and 17 died cases. The levels of PT, APTT, D-D, AT : A and PLG : A in the death group were lower than those in the survival group, while the Fib level was higher than that in the survival group. The results of ROC curve analysis showed that serum PT, APTT, Fib, TT and D-D were of predictive value for outcomes (AUC = 0.713, AUC = 0.683, AUC = 0.712, AUC = 0.761, AUC = 0.730, AUC = 0.765, AUC = 0.673, P < 0.05), and cutoff values were 20.29 s, 34.79 s, 3.54 g/L, 20.97 s, 1.42 μg/L, 73.53% and 63.97%, respectively. Conclusion There is coagulation and fibrinolysis dysfunction in patients with severe traumatic hemorrhagic shock, which is related to injury severity. The coagulation fibrinolysis indexes have a certain predictive value for outcomes of patients.

Mechanisms and prevention of intestinal barrier function damage in traumatic hemorrhagic shock

Mechanisms and prevention of intestinal barrier function damage in traumatic hemorrhagic shock

The conundrum of the definition of haemorrhagic shock: a pragmatic exploration based on a scoping review, experts’ survey and a cohort analysis

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

Damage Control Resuscitation in the Trauma Patient

Unintentional trauma is the leading cause of death among individuals younger than 45 years of age and the primary reason for productive years of life lost. 1 Centers for Disease and Control, Injury Prevention and Control. WISQUARS leading cause of death visualization tool. Available at: https://wisqars.cdc.gov/data/lcd/home Google Scholar Traumatic brain injury remains the greatest cause of traumatic death, however hemorrhage is considered the leading reason for preventable death from trauma with a fatality rate reaching 40%. 2 Owattanapanich N Chittawatanarat K Benyakorn T Sirikun J Risks and benefits of hypotensive resuscitation in patients with traumatic hemorrhagic shock: A meta-analysis. Scand J Trauma Resusc Emerg Med. 2018; 26 (Published 2018 Dec 17): 107https://doi.org/10.1186/s13049-018-0572-4 Crossref PubMed Scopus (36) Google Scholar Significant advances have been made over the last decades to reduce morbidity and mortality by shifting focus from treatment to stop the bleeding to that of rapid control of bleeding, establishing hemostasis, and stabilizing the patient until more definitive surgical treatment can be performed and is more likely to be successful. The procedure known as damage control surgery (DCS) first described in 1993 by Rotondo and et al 3 Rotondo MF Schwab CW McGonigal MD et al. “Damage control”: An approach for improved survival in exsanguinating penetrating abdominal injury. J Trauma. 1993; 35: 375-383 Crossref PubMed Scopus (1205) Google Scholar focuses on three principles: (1) Surgical control of hemorrhage and contamination with packing to establish hemostasis; (2) Effective resuscitation to reverse coagulopathies and acidosis, and stabilize the patient; and (3) Definitive surgical management when the patient is more stable. 3 Rotondo MF Schwab CW McGonigal MD et al. “Damage control”: An approach for improved survival in exsanguinating penetrating abdominal injury. J Trauma. 1993; 35: 375-383 Crossref PubMed Scopus (1205) Google Scholar , 4 Godat L Kobayashi L Costantini T Coimbra R Abdominal damage control surgery and reconstruction: World society of emergency surgery position paper. World J Emerg Surg. 2013; 8 (Published 2013 Dec 17): 53https://doi.org/10.1186/1749-7922-8-53 Crossref PubMed Scopus (69) Google Scholar , 5 Samuels JM Moore HB Moore EE Damage control resuscitation. Chirurgia (Bucur). 2017; 112: 514-523https://doi.org/10.21614/chirurgia.112.5.514 Crossref PubMed Scopus (17) Google Scholar DCS is predominately employed with patients who have major abdominal and thoracic injury, significant pelvic trauma, and/or multiple long bone fractures. 5 Samuels JM Moore HB Moore EE Damage control resuscitation. Chirurgia (Bucur). 2017; 112: 514-523https://doi.org/10.21614/chirurgia.112.5.514 Crossref PubMed Scopus (17) Google Scholar ,6 Ordoñez CA Parra MW Serna JJ et al. Damage control resuscitation: REBOA as the new fourth pillar. Colomb Med (Cali). 2020; 51 (Published 2020 Dec 30)e4014353https://doi.org/10.25100/cm.v51i4.4353 Crossref Scopus (12) Google Scholar

Combined Traumatic Brain Injury and Hemorrhagic Shock in Ferrets Leads to Structural, Neurochemical, and Functional Impairments.

Aeromedical evacuation-relevant hypobaria after traumatic brain injury (TBI) leads to increased neurological injury and death in rats relative to those maintained under normobaria. Applicability of rodent brain injury research to humans may be limited, however, by differences in neuroanatomy. Therefore, we developed a model in which ferrets are exposed to polytrauma consisting of controlled cortical impact TBI and hemorrhagic shock subjected 24 h later to 6 h of hypobaria or normobaria. Our objective was to determine whether the deleterious effects of hypobaria observed in rats, with lissencephalic brains, are also present in a species with a human-like gyrencephalic brain. While no deaths were observed, magnetic resonance spectroscopy (MRS) results obtained two days post-injury indicated reduced cortical creatine, N-acetylaspartate, gamma-aminobutyric acid, myo-inositol, and glutamate that were not affected by hypobaria. T2-weighted magnetic resonance imaging quantification revealed increased hyperintensity volume representing cortical edema at the site of impact after polytrauma. Hypobaria did not exacerbate this focal edema but did lead to overall reductions in total cortical volume. Both normobaric and hypobaric ferrets exhibited impaired spatial memory six days post-injury on the Object Location Test, but no differences were noted between groups. Finally, cortical lesion volume was not exacerbated by hypobaria exposure on day 7 post-injury. Results suggest that air travel 24 h after polytrauma is associated with structural changes in the ferret brain. Future studies should investigate secondary injury from hypobaria after polytrauma in greater detail including alternative outcome measures, time points, and exposure to multiple flights.

Zone 1 REBOA in a combat DCBI swine model does not worsen brain injury

BackgroundZone 1 resuscitative endovascular balloon occlusion of the aorta has been recommended for refractory shock after a dismounted complex blast injury for the austere combat scenario. While resuscitative endovascular balloon occlusion of the aorta should enhance coronary perfusion, there is a potential risk of secondary brain injury due to loss of cerebral autoregulation. We developed a combat casualty relevant dismounted complex blast injury swine model to evaluate the effects of resuscitative endovascular balloon occlusion of the aorta zone I on intracranial pressure and cerebral edema. We hypothesized that zone 1 aortic occlusion with resuscitative endovascular balloon occlusion of the aorta would increase mean arterial pressure transmitted in excessive intracranial pressure, thereby worsening brain injury. Methods50 kg male Yorkshire swine were subjected to a combination dismounted complex blast injury model consisting of blast traumatic brain injury (50 psi, ARA Mobile Shock Laboratory), tissue injury (bilateral femur fractures), and hemorrhagic shock (controlled bleeding to a base deficit goal of 10 mEq/L). During the shock phase, pigs were randomized to no aortic occlusion (n = 8) or to 30 minutes of zone 1 resuscitative endovascular balloon occlusion of the aorta (zone 1 aortic occlusion group, n = 6). After shock, pigs in both groups received a modified Tactical Combat Casualty Care–based resuscitation and were monitored for an additional 240 minutes until euthanasia/death for a total of 6 hours. Intracranial pressure was monitored throughout, and brains were harvested for water content. Linear mixed models for repeated measures were used to compare mean arterial pressure and intracranial pressure between zone 1 aortic occlusion and no aortic occlusion groups. ResultsAfter dismounted complex blast injury, the zone 1 group had a significantly higher mean arterial pressure during hemorrhagic shock compared to the control group (41.2 mm Hg vs 16.7 mm Hg, P = .002). During balloon occlusion, intracranial pressure was not significantly elevated in the zone 1 aortic occlusion group vs control, but intracranial pressure was significantly lower in the zone 1 group at the end of the observation period. In addition, the zone 1 aortic occlusion group did not have increased brain water content (zone 1 aortic occlusion: 3.95 ± 0.1g vs no aortic occlusion: 3.95 ± 0.3 g, P = .87). Troponin levels significantly increased in the no aortic occlusion group but did not in the zone 1 aortic occlusion group. ConclusionZone 1 aortic occlusion using resuscitative endovascular balloon occlusion of the aorta in a large animal dismounted complex blast injury model improved proximal mean arterial pressure while not significantly increasing intracranial pressure during balloon inflation. Observation up to 240 minutes postresuscitation did not show clinical signs of worsening brain injury or cardiac injury. These data suggest that in a dismounted complex blast injury swine model, resuscitative endovascular balloon occlusion of the aorta in zone 1 may provide neuro- and cardioprotection in the setting of blast traumatic brain injury. However, longer monitoring periods may be needed to confirm that the neuroprotection is lasting.

Effectiveness and safety of hypotension fluid resuscitation in traumatic hemorrhagic shock: A systematic review and meta-analysis of randomized controlled trials.

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

The Chemokine (C-C Motif) Receptor 2 Antagonist INCB3284 Reduces Fluid Requirements and Protects From Hemodynamic Decompensation During Resuscitation From Hemorrhagic Shock.

OBJECTIVES:Clinical correlations suggest that systemic chemokine (C-C motif) ligand (CCL) 2 release may contribute to blood pressure regulation and the development of hemodynamic instability during the early inflammatory response to traumatic-hemorrhagic shock. Thus, we investigated whether blockade of the principal CCL2 receptor chemokine (C-C motif) receptor (CCR) 2 affects blood pressure in normal animals, and hemodynamics and resuscitation fluid requirements in hemorrhagic shock models.DESIGN:Randomized prospective treatment study.SETTING:University laboratory.SUBJECTS:Male Sprague-Dawley rats.INTERVENTIONS:First, treatment of healthy anesthetized rats with increasing doses of INCB3284 or vehicle. Second, rats were hemorrhaged for 30 minutes, followed by treatment with the CCR2 antagonist INCB3284 (1.1 and 5.5 μmol/kg), the CCR5 antagonist Maraviroc (=control, 5.5 μmol/kg) or vehicle, and subsequent fluid resuscitation to maintain blood pressure until t = 90 minutes. Third, treatment of rats with 5 μmol/kg INCB3284 or vehicle after hemorrhage and fluid resuscitation until t = 300 minutes.MEASUREMENTS AND MAIN RESULTS:INCB3284 did not affect intrinsic function of isolated rat resistance arteries in pressure myography experiments. Blood pressure in anesthetized vehicle-treated animals continuously decreased by 0.09 ± 0.01 mm Hg/min (p < 0.001) but remained constant after INCB3284 injections. Systemic concentrations of the CCR2 agonists CCL2, CCL5, and CCL11 increased during hemorrhage and fluid resuscitation. INCB3284 dose-dependently reduced fluid requirements by 58% ± 11% in short-term experiments, whereas Maraviroc and vehicle-treated animals were indistinguishable. When resuscitation was performed until t = 300 minutes, INCB3284 reduced fluid requirements by 62% ± 6%, prevented from hemodynamic decompensation, reduced mortality from 50% with vehicle treatment to zero, and reduced overall tissue wet-weight/dry-weight ratios.CONCLUSIONS:Our findings suggest that CCR2 is involved in the regulation of normal cardiovascular function and during the cardiovascular stress response to hemorrhagic shock and fluid resuscitation. The present study identifies CCR2 as a drug target to reduce fluid requirements and to prevent death from hemodynamic decompensation during resuscitation from hemorrhagic shock.

Serum from rats subjected to traumatic brain injury and hemorrhagic shock induces profound endothelial barrier dysfunction

IntroductionTraumatic brain injury (TBI) has been associated with development of indirect acute respiratory distress syndrome (ARDS). However, the causative relationship between TBI and lung injury remains unclear. To explore potential mechanism linking TBI with development of ARDS, we characterized effects of serum factors released during TBI and hemorrhagic shock (HS) in a rat model on the pulmonary endothelial cell (EC) barrier dysfunction, a key feature of ARDS.MethodsThe adult male rat polytrauma model consisted of controlled cortical impact (CCI)–induced TBI followed by 30 minutes of hemorrhage shock (HS) induced by blood withdrawal. The HS phase was followed by a 1‐hour “prehospital” Hextend fluid resuscitation phase and then a 1‐hour “hospital phase” when shed blood was reinfused. 48 hours after the TBI, blood was drawn from right ventricle and serum samples were obtained. Serum was collected from the TBI or sham rats, and its effects on barrier properties of pulmonary endothelial cell culture were assessed by measurements of transendothelial electrical resistance (TER) using the electrical cell impedance sensor and visualization of fluorescent tracer penetration through EC monolayer using XPerT assay.ResultsWe found pronounced barrier‐disruptive effects of serum samples from animals exposed to controlled cortical impact (CCI) and HS, but not from sham operated rats. Rapid and sustained decrease in EC monolayer transendothelial resistance was observed within minutes after serum addition and remained below basal TER levels after incubation with CCI‐HS sera. Thrombin has been implicated in the early‐phase barrier disruptive activity of CCI‐HS serum, as both thrombin inhibitor and thrombin receptor antagonist attenuated the acute phase of serum‐induced TER decline, but did not affect TER decline at later time points. These findings suggest that thrombin elevation may play a role in early‐phase barrier disruptive activity of CCI‐HS serum. However, both the early and late phases of CCI‐HS‐induced EC permeability were inhibited by heparin. The late phase barrier disruptive effect of CCI‐HS was also prevented by serum preincubation with heparin‐sepharose. Pulmonary EC treated with serum from CCI‐HS rats for 3 hours have demonstrated significant decline in expression of EC junctional protein, VE‐Cadherin, and disassembly of peripheral EC adherens junction complexes monitored by immunostaining with VE‐cadherin antibody.ConclusionThese results suggest that exposure to CCI‐HS leads to production of humoral factors causing early and late‐phase barrier disruptive effects in lung vascular endothelium. While thrombin‐PAR1 signaling has been identified as mechanism of acute EC permeability increase by CCI‐HS serum, the factor(s) defining long‐term EC barrier disruption in CCI‐HS model remain to be determined.

Treatment with ddAVP improves platelet-based coagulation in a rat model of traumatic hemorrhagic shock

ObjectivesTrauma-induced hemorrhagic shock is characterized by increased endothelial permeability and coagulopathy. Vasopressin analog ddAVP (desmopressin) acts by reorganizing and redistributing adhesive and tight junction molecules, enhancing endothelial barrier function. Furthermore,...

Effect of Emergency Nursing on Patients with Severe Traumatic Hemorrhagic Shock

Effect of Emergency Nursing on Patients with Severe Traumatic Hemorrhagic Shock

The Protective Mechanism of Dexmedetomidine on Renal in Hemorrhagic Shock.

Objective To explore the protective effect of dexmedetomidine on renal function in patients with hemorrhagic shock and its possible mechanism. Methods Seventy patients with traumatic hemorrhagic shock requiring surgical treatment were randomly divided into the control group (group C) and the dexmedetomidine group (group D), with 35 patients in each group. Patients in both groups were actively treated with volumetric resuscitation while surgical hemostasis. Group D was given dexmedetomidine 0.5 μg/kg before skin incision after anesthesia induction, for 10 min, followed by intravenous infusion at a rate of 0.4 μg·kg−1·h−1 until 30 min before surgery, and group C was given equal volume of normal saline before skin resection (H1). Venous blood was collected 2 h (H2) and 4 h (H4) after skin resection, and plasma levels of BUN, creatinine (SCr), lipid peroxides (MDA), and inflammatory mediators IL-6 and IL-8 were measured on the 1st and 2nd day after surgery. Results Compared with H1, BUN and SCr levels had no significant difference at 2 h and 4 h after skin resection but significantly decreased at 1 and 2 postoperative days (D1) (P < 0.05). There were significant differences in MDA, IL-6, and IL-8 at 2 and 4 h after skin resection (P < 0.05), but there were no significant differences at 1 day after surgery (D1) and 2 days after surgery (D2). Compared with group C, the levels of MDA, IL-6, and IL-8 in group U were significantly decreased at 2 h and 4 h after skin resection (P < 0.05), and the levels of BUN and SCr in group U were significantly decreased at 1 and 2 days after skin resection (P < 0.05). Conclusion Dexmedetomidine can effectively inhibit the release of oxygen free radicals in the shock stage and the shock recovery stage in patients with hemorrhagic trauma shock and has a protective effect on renal function.

Protective effect of restrictive resuscitation on vascular endothelial glycocalyx in pigs with traumatic hemorrhagic shock.

BackgroundHemorrhagic shock is the leading cause of early traumatic death. Research and discussion on restrictive fluid resuscitation have been ongoing for many years. The purpose of this study was to explore whether restrictive resuscitation can inhibit the shedding of vascular endothelial glycocalyx in the prehospital treatment of traumatic hemorrhagic shock pigs.MethodsLandrace pigs were randomly divided into a restrictive resuscitation group (restrictive group) and a conventional resuscitation group (conventional group), with 6 pigs in each group. The gunshot caused a rupture of the pig’s receding right femoral artery, and the average arterial pressure was 40–45 mmHg stable for 30 minutes, which was defined as a successful shock model. The end point of resuscitation in the restrictive group was a mean arterial pressure (MAP) of 55–60 mmHg for 30 minutes, and the end point of resuscitation in the conventional group was a MAP of 70–75 mmHg for 30 minutes. The results of arterial blood gas analysis, hemodynamic indicators, endothelial glycocalyx damage and shedding marker Syndecan1 and soluble thrombomodulin (sTM) expression levels were compared between the two groups of experimental pigs after resuscitation.ResultsThe two groups of experimental pigs had the same baseline levels before injury in age, body weight, blood loss, cardiac output index, cardiac function index (CFI), extravascular lung water index (ELWI), and pulmonary vascular permeability index (PVPI). The arterial blood gas analysis of the two experimental pigs showed no significant difference in carbon dioxide partial pressure, oxygen partial pressure, blood oxygen saturation, or blood lactic acid after resuscitation. The difference in cardiac output index and CFI at the end of resuscitation between the two groups was not statistically significant; the absolute value and percentage of Syndecan1 level increase in the restrictive resuscitation group were lower than those in the conventional resuscitation group, and the difference was statistically significant.ConclusionsCompared with full resuscitation in a short period of prehospital treatment, restrictive resuscitation can achieve a similar effect in maintaining tissue oxygen supply and can reduce the loss of vascular endothelial glycocalyx to a certain extent.