ABSTRACT
OBJECTIVE: To study the biological role and related mechanism of autophagy in acute lung injury (ALI) of hemorrhagic shock mice. METHODS: According to random number table method, wild-type male C57BL/6 mice were divided into control group, ALI group, rapamycin group and 3-methyladenine (3-MA) group, with 8 mice in each group. Light chain 3 (LC3) gene knockout mice with C57BL/6 background were divided into LC3 knockout group and LC3 knockout+ALI group, with 8 mice in each group. Control group, ALI group, LC3 knockout group, LC3 knockout+ALI group were intraperitoneally injected with 2 mL/kg normal saline, rapamycin group was intraperitoneally injected with 3 mg/kg autophagy activator rapamycin, 3-MA group was intraperitoneally injected with 15 mg/kg autophagy inhibitor 3-MA, all of which were given for 3 consecutive days. 2 hours after the last administration, the hemorrhagic shock induced ALI model was established. 24 hours after modeling, the lung index was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue and lung injury score was performed. The expressions of autophagy genes LC3- II/LC3- I and Beclin-1 in lung tissue were detected by Western blotting. The contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in lung tissue were detected according to the steps of the kit. RESULTS: Compared with the control group, the lung tissue structure was destroyed and exudation increased, lung index, lung injury score, the expressions of LC3- II/LC3- I, Beclin-1, and the contents of TNF-α, IL-6 and MDA in lung tissue significantly increased in the ALI group. Compared with the ALI group, the structural damage and exudation of lung tissue were reduced in the rapamycin group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue decreased, while the expressions of LC3- II/LC3- I and Beclin-1 in lung tissue increased [lung index: (7.56±0.39)% vs. (9.12±0.59)%, lung injury score: 3.04±0.58 vs. 9.32±2.14, TNF-α (ng/mg): 1.85±0.32 vs. 3.51±0.62, IL-6 (ng/mg): 1.61±0.32 vs. 2.52±0.44, MDA (nmol/mg): 1.03±0.16 vs. 1.88±0.24, LC3- II/LC3- I: 1.21±0.12 vs. 0.39±0.05, Beclin-1/ß-actin: 1.10±0.12 vs. 0.58±0.06, all P < 0.05], while lung tissue structure damage was aggravated and exudation was further increased in the 3-MA group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue increased, the expressions of LC3- II/LC3- I and Beclin-1 in lung tissue decreased [lung index: (10.44±0.62)% vs. (9.12±0.59)%, lung injury score: 11.59±2.28 vs. 9.32±2.14, TNF-α (ng/mg): 4.77±0.71 vs. 3.51±0.62, IL-6 (ng/mg): 3.44±0.52 vs. 2.52±0.44, MDA (nmol/mg): 2.71±0.42 vs. 1.88±0.24, LC3- II/LC3- I: 0.25±0.04 vs. 0.39±0.05, Beclin-1/ß-actin: 0.21±0.03 vs. 0.58±0.06, all P < 0.05]. Lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue of LC3 knockout ALI mice were higher than those of wild-type ALI mice [lung index: (10.44±0.75)% vs. (9.12±0.59)%, lung injury score: 12.41±2.86 vs. 9.32±2.14, TNF-α (ng/mg): 4.85±0.72 vs. 3.51±0.62, IL-6 (ng/mg): 3.28±0.51 vs. 2.52±0.44, MDA (nmol/mg): 2.75±0.41 vs. 1.88±0.24, all P < 0.05]. CONCLUSIONS: Autophagy plays a protective role in ALI of hemorrhagic shock mice, and the related molecular mechanism is the inhibition of inflammatory response and oxidative stress response.
Subject(s)
Acute Lung Injury , Autophagy , Interleukin-6 , Mice, Inbred C57BL , Mice, Knockout , Shock, Hemorrhagic , Tumor Necrosis Factor-alpha , Animals , Acute Lung Injury/metabolism , Male , Shock, Hemorrhagic/metabolism , Shock, Hemorrhagic/complications , Mice , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Disease Models, Animal , Lung/metabolism , Lung/pathology , Microtubule-Associated Proteins/metabolismABSTRACT
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 â¼50 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.
Subject(s)
Adenosine , Hypotension , Resuscitation , Animals , Swine , Resuscitation/methods , Rats , Hypotension/etiology , Hypotension/physiopathology , Adenosine/administration & dosage , Adenosine/pharmacology , Lidocaine/pharmacology , Lidocaine/therapeutic use , Lidocaine/administration & dosage , Female , Shock, Hemorrhagic/therapy , Shock, Hemorrhagic/complications , Shock, Hemorrhagic/physiopathologyABSTRACT
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.
Subject(s)
Apoptosis , Shock, Hemorrhagic , Shock, Hemorrhagic/therapy , Shock, Hemorrhagic/complications , Shock, Hemorrhagic/immunology , Animals , Rats , Male , Apoptosis/physiology , Rats, Sprague-Dawley , Disease Models, Animal , Cell- and Tissue-Based Therapy/methods , Cytokines/blood , Cytokines/analysis , Inflammation/therapyABSTRACT
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 â¼1 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.
Subject(s)
Cerebrovascular Circulation , Hypoxia , Shock, Hemorrhagic , Spectroscopy, Near-Infrared , Animals , Shock, Hemorrhagic/physiopathology , Shock, Hemorrhagic/complications , Shock, Hemorrhagic/diagnosis , Shock, Hemorrhagic/therapy , Shock, Hemorrhagic/etiology , Swine , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/instrumentation , Cerebrovascular Circulation/physiology , Hypoxia/physiopathology , Hypoxia/etiology , Hypoxia/complications , Monitoring, Physiologic/methods , Monitoring, Physiologic/instrumentation , Hemodynamics/physiology , Disease Models, AnimalABSTRACT
Vitamin K is an essential dietary cofactor required for the synthesis of active forms of vitamin K-dependent procoagulant proteins. Vitamin K deficiency, particularly late-onset deficiency occurring between 1 week and 6 months of age, can cause a life-threatening bleeding disorder. An exclusively breastfed, full-term, 6-week-old infant male presented with severe haemorrhagic shock and multi-system organ failure related to caregiver refusal of intramuscular vitamin K after birth. Coagulation studies were normalised within 8 hours of intramuscular vitamin K administration. An increasing number of caregivers are refusing intramuscular vitamin K which has led to a rise in the incidence of vitamin K deficiency bleeding. Health policy organisations around the world emphasise the benefits of intramuscular vitamin K and risks of refusal, particularly in exclusively breastfed infants who are at higher risk due to low vitamin K levels in breast milk. This case highlights the multi-system severity of this life-threatening yet preventable disorder.
Subject(s)
Multiple Organ Failure , Shock, Hemorrhagic , Vitamin K Deficiency , Vitamin K , Humans , Male , Multiple Organ Failure/etiology , Vitamin K Deficiency/complications , Infant , Shock, Hemorrhagic/etiology , Vitamin K/therapeutic use , Vitamin K/administration & dosage , Breast Feeding , Vitamin K Deficiency Bleeding/diagnosis , Injections, Intramuscular , Treatment RefusalABSTRACT
RATIONALE: Postoperative bleeding after lobectomy is relatively rare. By analyzing and discussing the case history and management of hemorrhagic shock caused by chest tube removal after lobectomy, we can achieve the purpose of preventing postoperative bleeding after thoracic surgery and reducing postoperative complications, which can help avoid the risk of second surgery, shorten the patient's hospital stay, reduce the cost of medical care, and improve the patient's quality of life. PATIENT CONCERNS: A case of bleeding from tube removal after lobectomy. The bleeding from chest drain removal on the 3rd day after thoracoscopic lobectomy resulted in hemorrhagic shock, which was stopped by thoracoscopic exploration again under active antishock, and there was no recurrence of bleeding after the operation, and the patient was discharged from the hospital after chest drain removal. DIAGNOSES: Enhanced computed tomography of the chest revealed a space-occupying lesion in the middle lobe of the right lung. INTERVENTIONS: Thoracoscopy was performed again on the condition of active anti-shock. OUTCOMES: On the third day after thoracoscopic lobectomy, the patient underwent removal of the chest drain and subsequently experienced hemorrhagic shock. Given the necessity of maintaining anti-shock measures, the patient was subjected to a second thoracoscopic exploration with the objective of halting the hemorrhage. Following this procedure, the patient did not present with any further episodes of bleeding. Subsequently, a new chest drain was placed, and once the drainage flow had diminished to an acceptable level, the chest drain was removed. The patient subsequently made a full recovery and was discharged from the hospital. LESSONS: Even if the safely inserted drain tube is removed, the thoracic surgeon must be aware of possible vascular bleeding.
Subject(s)
Chest Tubes , Device Removal , Pneumonectomy , Postoperative Hemorrhage , Humans , Chest Tubes/adverse effects , Device Removal/methods , Pneumonectomy/adverse effects , Pneumonectomy/methods , Male , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/therapy , Thoracoscopy/methods , Thoracoscopy/adverse effects , Shock, Hemorrhagic/etiology , Drainage/methods , Lung Neoplasms/surgery , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: Treatment of hemorrhagic shock (HS) induced multi-organ injury remains a challenge. Bergapten (BeG) is a bioactive coumarin-derived compound, and previous articles have suggested that BeG may serve as a prospective therapeutic modality for HS. This study was designed to investigate the efficacy of BeG in the treatment of HS and its underlying mechanisms. METHODS: In this research, we established a rat model of HS, following which we assessed the protective effects of BeG on HS induced multi-organ injury. Subsequently, we scrutinized the activation of NLRP3 inflammasomes and pyroptosis in damaged organs. Additionally, we conducted examinations of AMPK and the downstream mitophagy pathway in damaged organs. Finally, we established a hypoxia/reoxygenation (H/R) model in HK-2 cells to simulate the in vitro HS process. Following AMPK inhibition with compound C, we evaluated the levels of mitophagy and cellular pyroptosis in BeG-treated HK-2 cells subjected to H/R. RESULTS: BeG treatment alleviated HS induced multi-organ injury. Subsequent analyses indicated that the therapeutic effects of BeG were related to the attenuation of NLRP3 inflammasome activation and pyroptosis. Additionally, we found BeG treatment stimulated the phosphorylation of AMPK, thereby enhancing mitophagy. Lastly, we found that the inhibition of AMPK in vitro attenuates BeG's enhancement of mitophagy and its suppression of pyroptosis. CONCLUSION: Our research indicates that BeG has the potential to alleviate multi-organ injury induced by HS. The protective effect of BeG is likely associated with its promotion of mitophagy through AMPK activation, thereby inhibiting NLRP3 inflammasome-mediated pyroptosis.
Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Rats, Sprague-Dawley , Shock, Hemorrhagic , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/complications , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis/drug effects , Humans , Male , Inflammasomes/metabolism , Cell Line , Rats , Coumarins/pharmacology , Coumarins/therapeutic use , Mitophagy/drug effects , AMP-Activated Protein Kinases/metabolism , Disease Models, Animal , Multiple Organ Failure/drug therapy , Multiple Organ Failure/prevention & control , Multiple Organ Failure/etiologyABSTRACT
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 <50â¯mmHg was reached or 40â¯% of the estimated blood volume was removed. Canines were left in shock for 45â¯mins before being resuscitated with one of the resuscitation fluids over 30â¯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 24â¯hr compared to baseline (p<0.001). Hyaluronan was significantly elevated by 3â¯hr in all cases (p<0.01), except for HBOC fluids. Total glycosaminoglycans were significantly reduced only at 3â¯hr (p<0.001) for non-HBOC fluids. Similarly, heparan sulfate was significantly reduced with all fluids between resuscitation and 24â¯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.
Subject(s)
Dog Diseases , Fluid Therapy , Glycocalyx , Resuscitation , Shock, Hemorrhagic , Animals , Dogs , Glycocalyx/metabolism , Resuscitation/veterinary , Resuscitation/methods , Shock, Hemorrhagic/veterinary , Shock, Hemorrhagic/therapy , Fluid Therapy/veterinary , Dog Diseases/therapy , Male , Female , Disease Models, Animal , Biomarkers/blood , Syndecan-1/metabolismABSTRACT
Background: Male circumcision (MC) is a practice involving the surgical excision of the foreskin to expose the glans and it is often performed for religious reasons. Ritual circumcision is frequently carried out by unqualified practitioners in inadequate settings, which can also lead to the death of the individual. Case Report: A 28-day-old infant was undergoing circumcision by a man that performed the circumcision using a razor blade. During the same day, the child experienced continuous bleeding from the wound and, finally, died after about 20 hours. At autopsy, a cutaneous sharp injury was revealed with ablation of the foreskin and part of the penile body. The lesion had irregular and jagged margins, with diffuse hemorrhagic infiltration. The glans and upper fascia of the penis appeared edematous and hyperemic and there were abundant hemorrhagic infiltrations in the frenulum area. The child's death was attributed to hemorrhagic shock in a child undergoing genital mutilation surgery. The finding of a significant hemorrhagic infiltration of the frenulum region indicated that the frenular artery had been severed. Conclusions: Around 35% of ritual male circumcisions are performed clandestinely in Italy, and typically by unqualified practitioners. In such events, the forensic investigation of the injuries inflicted on the victim allows for determining whether the procedure was performed appropriately or not, to verify the existence of a causal link between the procedure itself and the death of the individual.
Subject(s)
Ceremonial Behavior , Circumcision, Male , Shock, Hemorrhagic , Humans , Circumcision, Male/adverse effects , Male , Shock, Hemorrhagic/etiology , Fatal Outcome , Infant, NewbornABSTRACT
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.
Subject(s)
Fiber Optic Technology , Intubation, Intratracheal , Multiple Trauma , Humans , Male , Prone Position , Intubation, Intratracheal/methods , Multiple Trauma/surgery , Wakefulness , Adult , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/surgery , Shock, Hemorrhagic/therapy , Patient Positioning/methodsABSTRACT
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.
Subject(s)
Blood Transfusion , Wounds and Injuries , Humans , Retrospective Studies , Male , Female , Middle Aged , Adult , Blood Transfusion/methods , Blood Transfusion/statistics & numerical data , Blood Transfusion/trends , Wounds and Injuries/mortality , Wounds and Injuries/therapy , Wounds and Injuries/blood , Cohort Studies , Logistic Models , Shock, Hemorrhagic/mortality , Shock, Hemorrhagic/therapy , Mortality/trendsABSTRACT
INTRODUCTION: hemorrhagic shock is a significant cause of trauma-related deaths in Brazil and worldwide. This study aims to compare BE and lactate values at ICU admission and twenty-four hours after in identifying tissue hypoperfusion and mortality. METHODS: examines a historical cohort of trauma patients over eitheen years old submittet to damage control resuscitation approch upon hospital admission and were then admitted to the ICU. We collected and analyzed ISS, mechanism and type of trauma, need for renal replacement therapy, massive transfusion. BE, lactate, pH, bicarbonate at ICU admission and twenty-four hours later, and mortality data. The patients were grouped based on their BE values (≥-6 and <-6mmol/L), which were previously identified in the literature as predictors of severity. They were subsequently redivided using the most accurate values found in this sample. In addition to performing multivariate binary logistic regression. The data were compared using several statistical tests due to diversity and according to the indication for each variable. RESULTS: there were significant changes in perfusion upon admission to the Intensive Care Unit. BE is a statistically significant value for predicting mortality, as determined by using values from previous literature and from this study. CONCLUSION: the results demonstrate the importance of monitoring BE levels in the prediction of ICU mortality. BE proves to be a valuable bedside marker with quick results and wide availability.
Subject(s)
Biomarkers , Lactic Acid , Shock, Hemorrhagic , Humans , Shock, Hemorrhagic/mortality , Shock, Hemorrhagic/blood , Male , Female , Lactic Acid/blood , Adult , Biomarkers/blood , Middle Aged , Cohort Studies , Intensive Care UnitsABSTRACT
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.
Subject(s)
Ferroptosis , Myocytes, Cardiac , Nanoparticles , Shock, Hemorrhagic , Animals , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/therapy , Rats , Ferroptosis/drug effects , Male , Myocytes, Cardiac/drug effects , Nanoparticles/chemistry , Resuscitation/methods , Rats, Sprague-Dawley , Cell Line , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Cyclooxygenase 2/metabolism , Lipid Peroxidation/drug effects , Oxidative Stress/drug effectsABSTRACT
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.
Subject(s)
Embolization, Therapeutic , Fractures, Bone , Pelvic Bones , Humans , Embolization, Therapeutic/methods , Embolization, Therapeutic/instrumentation , Pelvic Bones/injuries , Pelvic Bones/diagnostic imaging , Fractures, Bone/therapy , Fractures, Bone/complications , Male , Adult , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/therapy , Iliac Artery/injuries , Iliac Artery/diagnostic imaging , Fatal Outcome , Accidents, Traffic , AngiographyABSTRACT
Hemorrhagic shock (HS), a leading cause of preventable death, is characterized by severe blood loss and inadequate tissue perfusion. Reoxygenation of ischemic tissues exacerbates organ damage through ischemia-reperfusion injury. SUMOylation has been shown to protect neurons after stroke and is upregulated in response to cellular stress. However, the role of SUMOylation in organ protection after HS is unknown. This study aimed to investigate SUMOylation-mediated organ protection following HS. Male Wistar rats were subjected to HS (blood pressure of 40 ± 2 mmHg, for 90 min) followed by reperfusion. Blood, kidney, and liver samples were collected at various time points after reperfusion to assess organ damage and investigate the profile of SUMO1 and SUMO2/3 conjugation. In addition, human kidney cells (HK-2), treated with the SUMOylation inhibitor TAK-981 or overexpressing SUMO proteins, were subjected to oxygen and glucose deprivation to investigate the role of SUMOylation in hypoxia/reoxygenation injury. The animals presented progressive multiorgan dysfunction, except for the renal system, which showed improvement over time. Compared to the liver, the kidneys displayed distinct patterns in terms of oxidative stress, apoptosis activation, and tissue damage. The global level of SUMO2/3 in renal tissue was also distinct, suggesting a differential role. Pharmacological inhibition of SUMOylation reduced cell viability after hypoxia-reoxygenation damage, while overexpression of SUMO1 or SUMO2 protected the cells. These findings suggest that SUMOylation might play a critical role in cellular protection during ischemia-reperfusion injury in the kidneys, a role not observed in the liver. This difference potentially explains the renal resilience observed in HS animals when compared to other systems.
Subject(s)
Rats, Wistar , Shock, Hemorrhagic , Sumoylation , Animals , Male , Shock, Hemorrhagic/metabolism , Sumoylation/drug effects , Sumoylation/physiology , Rats , Humans , Kidney/metabolism , Kidney/pathology , Kidney/drug effects , Reperfusion Injury/metabolism , Cell LineABSTRACT
We report an autopsy of a death due to a ruptured infected pseudoaneurysm; a man in his 70s was found dead with massive bleeding from the shunt of his right arm. Autopsy and pathological examination revealed that the cause of death was hemorrhagic shock due to rupture of an infected pseudoaneurysm. Ruptured aneurysms and pseudoaneurysm are a complication of dialysis, and death is rare because they are treated immediately on discovery. However, these ruptures often occur in non-medical facilities and could result in death if the patient does not have knowledge of first aid. Thus, patient education is important. Approximately only half of the deaths due to massive bleeding from a shunt are autopsied. In Japan, autopsies or partial autopsies are considered necessary to determine whether a bleeding was traumatic and to prevent medical errors from being overlooked.
Subject(s)
Aneurysm, False , Humans , Aneurysm, False/etiology , Male , Aged , Autopsy , Aneurysm, Ruptured , Arteriovenous Shunt, Surgical/adverse effects , Shock, Hemorrhagic/etiology , Renal Dialysis/adverse effects , Hemorrhage/etiology , Fatal Outcome , Aneurysm, InfectedABSTRACT
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.
Subject(s)
Rats, Sprague-Dawley , Resuscitation , Shock, Hemorrhagic , Animals , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/therapy , Shock, Hemorrhagic/metabolism , Rats , Resuscitation/methods , Male , Colon/drug effects , Colon/pathology , Colon/metabolism , Inflammation/drug therapy , Carbon Monoxide/pharmacology , Carbon Monoxide/metabolism , Hemoglobins , Oxidative Stress/drug effectsABSTRACT
Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < PaO2 < 250 mmHg vs. normoxemia 80 < PaO2 < 120 mmHg) coincided with improved neurological function. Since brain perfusion, oxygenation and metabolism did not differ, this post hoc study analyzed the available material for the effects of targeted hyperoxemia on cerebral tissue markers of oxidative/nitrosative stress (nitrotyrosine expression), blood-brain barrier integrity (extravascular albumin accumulation) and fluid homeostasis (oxytocin, its receptor and the H2S-producing enzymes cystathionine-ß-synthase and cystathionine-γ-lyase). After 2 h of ASDH + HS (0.1 mL/kgBW autologous blood injected into the subdural space and passive removal of 30% of the blood volume), animals were resuscitated for up to 53 h by re-transfusion of shed blood, noradrenaline infusion to maintain cerebral perfusion pressure at baseline levels and hyper-/normoxemia during the first 24 h. Immediate postmortem, bi-hemispheric (i.e., blood-injected and contra-lateral) prefrontal cortex specimens from the base of the sulci underwent immunohistochemistry (% positive tissue staining) analysis of oxidative/nitrosative stress, blood-brain barrier integrity and fluid homeostasis. None of these tissue markers explained any differences in hyperoxemia-related neurological function. Likewise, hyperoxemia exerted no deleterious effects.
Subject(s)
Brain , Hematoma, Subdural, Acute , Shock, Hemorrhagic , Animals , Swine , Hematoma, Subdural, Acute/metabolism , Hematoma, Subdural, Acute/etiology , Hematoma, Subdural, Acute/pathology , Shock, Hemorrhagic/metabolism , Brain/metabolism , Brain/pathology , Blood-Brain Barrier/metabolism , Immunohistochemistry , Oxidative Stress , Resuscitation/methods , Disease Models, Animal , Oxygen/metabolism , Tyrosine/analogs & derivatives , Tyrosine/metabolismABSTRACT
Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.