Search Results (41)

Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection and progressive organ dysfunction. Although early antimicrobial therapy, source control, hemodynamic resuscitation, and organ support remain the foundations of care, these approaches do not directly reverse the cellular mechanisms that connect systemic inflammation to multi-organ failure. Mitochondrial dysfunction has emerged as a central mechanism linking impaired oxygen utilization, oxidative and nitrosative stress, immune-cell metabolic reprogramming, inflammatory amplification, and organ injury. During sepsis, inflammatory mediators, nitric oxide, microcirculatory abnormalities, calcium dysregulation, and metabolic stress converge on mitochondria, impairing oxidative phosphorylation and promoting mitochondrial reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. When mitochondrial quality-control programs, including fission, fusion, mitophagy, and mitochondrial biogenesis, fail to restore network integrity, damaged mitochondria accumulate and become persistent sources of oxidative stress and danger signals. Mitochondrial damage-associated molecular patterns, particularly mitochondrial DNA, oxidized mitochondrial DNA, cardiolipin, ATP, and N-formyl peptides, activate innate immune pathways such as TLR9-MyD88-NF-kappaB, the NLRP3 inflammasome, and cGAS-STING signaling. In parallel, mitochondrial metabolism shapes macrophage activation, neutrophil function, T-cell competence, pyruvate-lactate handling through the pyruvate dehydrogenase complex, and the transition between hyperinflammation and immunosuppression. Clinical translation remains challenging because sepsis is biologically heterogeneous and mitochondrial dysfunction is dynamic, tissue-specific, and influenced by disease stage. This review synthesizes current knowledge on mitochondrial dysfunction in sepsis, emphasizing oxidative and nitrosative stress, mitochondrial quality control, mitochondrial damage-associated molecular pattern (DAMP) signaling, immunometabolism, organ-specific injury, candidate biomarkers, clinical translational strategies for mitochondria-targeted therapy, and future approaches based on multi-omics and artificial intelligence-assisted patient stratification. We argue that future therapeutic development should move beyond nonspecific antioxidant supplementation toward time-sensitive, phenotype-informed, and biomarker-guided mitochondrial medicine. Full article

Background and Objectives: Traumatic hemorrhage remains the leading cause of preventable death following major injury, with most hemorrhage-related fatalities occurring within the first hours after trauma. During this early phase, trauma-induced coagulopathy (TIC) frequently develops as an independent pathophysiological response, affecting up to one-third of severely injured patients and being strongly associated with increased morbidity and mortality. Over the past two decades, TIC has been recognized as a complex endogenous process rather than a simple consequence of dilution, hypothermia, or acidosis, prompting a paradigm shift in early trauma resuscitation. Materials and Methods: This narrative review analyzes the current literature on the pathophysiology of TIC and the evolution of hemostatic resuscitation strategies. Key topics include the mechanisms underlying early coagulopathy, its clinical impact, and the evidence supporting contemporary therapeutic approaches. Published data on balanced transfusion strategies, whole blood transfusion, fibrinogen replacement, cryoprecipitate, prothrombin complex concentrates, tranexamic acid and viscoelastic-guided resuscitation were reviewed, along with relevant international guidelines. Results: Emerging evidence supports early, balanced, and targeted hemostatic resuscitation to mitigate the effects of TIC and improve outcomes in bleeding trauma patients. Balanced transfusion ratios, prompt correction of fibrinogen deficiency, early antifibrinolytic therapy and selective use of coagulation factor concentrates have been associated with reduced transfusion requirements and improved survival. Viscoelastic testing enables rapid, individualized assessment of coagulation abnormalities, although its availability and implementation remain inconsistent across trauma systems. Conclusions: Early recognition and aggressive, structured management of trauma-induced coagulopathy are essential to reduce preventable deaths from traumatic hemorrhage. While advances in hemostatic resuscitation have improved outcomes, significant challenges remain in standardizing treatment protocols and expanding access to viscoelastic diagnostics. Ongoing research and system-level optimization are needed to further refine and disseminate evidence-based strategies for the management of TIC. Full article

Background/Objectives: Damage Control Resuscitation (DCR) is a critical strategy in the management of severe trauma, focusing on the optimisation of the patient’s physiological condition. This study reviews current DCR strategies, emphasizing the mitigation of the “diamond of death”—hypothermia, acidosis, coagulopathy, and hypocalcemia—while addressing complex disturbances like respiratory distress syndrome (ARDS) and (acute kidney injury) AKI in high-ISS (Injury Severity Score) patients. Methods: A systematic review of 59 contemporary sources was conducted, encompassing clinical trials (e.g., CRASH-2), military-to-civilian protocol translations, and guidelines from the C and European Resuscitation Council. The analysis focused on pre-hospital interventions, in-hospital transfusion protocols, and the impact of transport logistics on survival. Results: Evidence highlights that aggressive crystalloid resuscitation (over 5 L) significantly increases mortality, favoring balanced blood component therapy (1:1:1 ratio) or Whole Blood guided by viscoelastic testing like rotational thromboelastometry (ROTEM) or thromboelastography (TEG). Pre-hospital success is driven by rapid hemorrhage control via tourniquets, early administration of Tranexamic Acid (TXA), no aggressive crystalloids, permissive hypotension, proactive calcium supplementation is recommended in early care. Furthermore, the integration of Helicopter Emergency Medical Services (HEMS) is independently associated with improved survival in multi-organ trauma by reducing time to definitive care and facilitating “en-route” damage control. Conclusions: The evolution of rescue strategies focused on mitigating the effects of the diamond of death, combined with the implementation of permissive hypotension and optimized HEMS logistics, constitutes the foundation of a modern model aimed at minimizing mortality in multi-organ trauma. Full article

Introduction: Severe traumatic brain injury (sTBI) frequently coexists with polytrauma and often necessitates damage control neurosurgery (DCNS), where rapid decompression and temporary stabilization take precedence over definitive reconstruction. Within this context, anesthetic management must balance cerebral protection with ongoing resuscitation, yet high-quality DCNS-specific evidence remains limited. Materials and Methods: A comprehensive search of PubMed, Scopus, and Google Scholar (2015–2025) was conducted using MeSH terms and keywords related to neurotrauma, anesthesia, intracranial pressure, and perioperative management. Studies were included if they examined anesthetic or hemodynamic strategies in severe TBI or DCNS and reported relevant clinical or physiologic outcomes. Results: Nineteen articles addressing perioperative strategies for optimizing DCNS outcomes were analyzed. Discussion: Preoperative care emphasizes hemodynamic stabilization and permissive hypertension, damage control resuscitation including massive transfusion protocols, optimization of cerebral perfusion pressure (CPP) and neuromonitoring, and the use of hyperosmolar therapy. Transexamic acid can be used in sTBI safely but with unclear improvement in outcomes. Intraoperatively, propofol-based total intravenous anesthesia is generally preferred over volatile agents due to favorable effects on intracranial pressure (ICP), cerebral blood flow (CBF), autoregulation, and emergence. While historically contraindicated, ketamine and etomidate are now increasingly used as hemodynamically protective induction agents. Analgesic and sedative strategies prioritize dexmedetomidine and carefully titrated opioids to minimize respiratory depression and reduce postoperative complications. CPP and ICP-directed management relies on individualized blood pressure targets, vasopressor selection, lung-protective ventilation, and strict temperature control. Conclusions: Emerging evidence has suggested the benefit of DCNS for patient survival. Overall, perioperative care is guided largely by physiology and extrapolation, highlighting the need for standardized protocols. Full article

High-energy ballistic and avulsive injuries to the face represent some of the most complex challenges in modern reconstructive surgery. Since Robertson and Manson’s 1999 management protocol, extensive military experience and technological advancements have transformed the treatment principles while preserving the core tenets of staged care. This updated review synthesizes evidence from 36 studies published since 2000, encompassing over two decades of global experience in both military and civilian trauma. Advances in damage-control resuscitation, wound decontamination, and early skeletal stabilization have improved survival and functional outcomes. Modern imaging—particularly intraoperative CT and navigation—enables the precise verification of the reduction and removal of retained fragments, while virtual surgical planning and patient-specific implants allow the accurate restoration of facial buttresses. Early vascularized tissue transfer has reduced contracture and infection rates. Adjuncts such as hyperbaric oxygen therapy, permissive hypotension, and advanced hemostatic agents further optimize recovery. The updated four-phase protocol—resuscitation, reconstitution, reconstruction, and rehabilitation—emphasizes early definitive repair, multidisciplinary collaboration, and the integration of digital planning. These refinements extend Robertson and Manson’s foundational principles into the era of precision surgery, achieving superior aesthetic and functional outcomes for patients with devastating facial injuries. Full article

Introduction: Currently, REBOA (Resuscitative Endovascular Balloon Occlusion of the Aorta) is an emerging technique for resuscitation in patients presenting severe pathology in hemodynamic shock refractory to conventional treatments. The REBOA technique consists of inserting a balloon through the femoral artery to temporarily occlude the aorta and thus control massive bleeding and improve perfusion of vital organs in critical situations such as hemorrhagic shock. Although it is not a definitive technique, its use buys time before the implementation of a definitive treatment when possible. This makes REBOA an ideal technique for the philosophy of out-of-hospital emergency services and more particularly in the HEMS (Helicopter Emergency Medical Service) environment. On the other hand, REBOA has been postulated as one of the basic pillars in the resuscitation of severe trauma patients with hemorrhagic shock and of the doctrine of damage-control resuscitation in non-compressible torso and lower limb hemorrhage. Objective: To evaluate the potential feasibility of REBOA implementation in patients attended by HEMS teams in Castilla-La Mancha, Spain. Method: A retrospective observational study was conducted analyzing medical and nursing reports from HEMS units between 1 January and 31 December 2023. A statistical study of the variables collected was carried out using statistical techniques appropriate to the pre-specified study variables. A descriptive analysis of the population was performed. Frequency results are expressed in absolute terms, as percentages and confidence intervals. Continuous variables are expressed as mean (SD) and median (range) according to normality test (Kolmogorov–Smirnov test). For the study of the relationship between the different variables, Chi-square or Analysis of Variance is used if they are parametric. Descriptive and inferential statistics were performed using SPSS v24. Results: A total of 103 patients (72.81% men, mean age 57.7 years) were identified as potential REBOA candidates. On arrival of the emergency services the mean SI (shock index) of the patients was 1.36 (SD +/− 0.380). On arrival at the hospital, the mean SI was 1.25 (SD +/− 0.601). Of the series, 57 (55.33%) patients suffered cardiorespiratory arrest (CRA) at some point during pre-hospital care. Of the total number of patients, 38 were patients presenting severe trauma criteria (characterized by life-threatening injuries, with RTS score ≤ 11, shock index > 0.9, or ISS ≥ 16, indicating severe physiological or anatomical alterations), of which 26 (68.4%) did not go into CRA, while 12 (31.6%) did. Of the total number of patients, 65 (63.1%) did not meet severe trauma criteria, but did present medical criteria for REBOA placement, of which 55 (53.4%) were patients who at some point during attendance presented CRA. Although the shock index showed a slight decrease after healthcare without statistical significance or relevant correlation, a highly significant association was observed between severe trauma and cardiorespiratory arrest (p < 0.001). Conclusions: It could be affirmed that it may have been feasible to implement REBOA in 4.47% (103) of the patients attended by the HEMS healthcare team of Castilla-La Mancha. This could help to reduce the morbimortality and mortality of critical patients in medical helicopters. More studies are needed to corroborate this assertion. Full article

Background: A major challenge in developing effective immunological damage-control therapies for traumatic hemorrhage (TH) is the lack of animal models that accurately reproduce the immune and pathophysiological responses observed in humans. In this study, we established a clinically relevant rat model that combines blast injury with hemorrhagic shock in a simulated prolonged damage control resuscitation environment. Methods: Male Sprague Dawley rats were anesthetized and subjected to moderate blast overpressure, followed by controlled hemorrhage equivalent to 40% of the estimated total blood volume. Animals then received hypotensive resuscitation with Plasma-Lyte A at twice the shed blood volume. Plasma-Lyte A was used in our study to correct hypovolemia and electrolyte imbalances, thereby helping to standardize the traumatic hemorrhage model. Results: Four of six rats in the blast-plus-hemorrhage (B + H) group survived the 25 h observation period. During resuscitation, mean arterial pressure remained markedly below baseline for at least 4 h. The B + H insult triggered a rapid innate immune response, characterized by elevated circulating HMGB1, terminal complement activation, and increased myeloperoxidase levels. Complement deposition (C4d, C5a, and C5b-9) was evident in lung tissue, accompanied by multi-organ histopathological injury, including pronounced inflammatory cell infiltration, hemorrhage, and cellular degeneration, apoptosis, or necrosis. Metabolic disturbances, including acidosis, hyperkalemia, and dilutional anemia, were also observed. Conclusions: Overall, this model reproduced key features of inflammation-driven multi-organ dysfunction syndrome seen in human polytrauma, supporting its utility for studying TH-related immunopathology and therapeutic interventions during prolonged damage control resuscitation. Full article

Acute lung injury may occur after cardiac arrest (CA), with innate immunity likely playing an important role in lung inflammation after CA. This study aimed to survey serial changes in the toll-like receptor (TLR) 4 signaling pathway in post-resuscitation lung injury in CA rats. A randomized animal study was conducted in rats with CA followed by successful cardiopulmonary resuscitation (CPR). The expression of TLR4 pathway biomarkers was analyzed and compared to the sham controls at different time points after CA with CPR. Lung tissues were collected for histological analysis to assess structural damage. Bronchoalveolar lavage fluid (BALF) was analyzed to quantify inflammatory cytokines and to assess changes in regulatory B cells (Bregs) and regulatory T cells (Tregs). Histological examination revealed marked pulmonary hemorrhage and structural injury shortly after CA. CA with CPR increased myeloid differentiation factor 88 (MyD88) mRNA and protein expression compared to controls at 2 h after CA. Cytokine analysis of BALF showed elevated IFN-γ, interleukin (IL)-1α, IL-1β, IL-2, IL-6, and IL-10 at 2 h after CA. A reduction in Bregs was noted at 2 h, whereas Tregs transiently increased between 2 and 4 h but declined at 6 h after CA. The MyD88-dependent signaling pathway appears to be rapidly activated in rats with CA after CPR, which may contribute to the early pulmonary inflammation observed as soon as 2 h after CA. Full article

Background: Traumatic injuries of the duodenum are generally rare but when they occur, they can result in serious complications. Inaccurate injury classification, delayed diagnosis, or late treatment can significantly raise morbidity and mortality. A multidisciplinary approach is often necessary. Mechanisms of injury: Isolated duodenal injuries are relatively uncommon due to the duodenum’s proximity to pancreas and major vascular structures. Duodenal injuries can result from blunt or penetrating trauma. Classification: The 2019 World Society of Emergency Surgery (WSES)-American Association for the Surgery of Trauma (AAST) guidelines recommend incorporating both the AAST-OIS grading and the patient’s hemodynamic status to stratify duodenal injuries into four categories: Minor injuries WSES class I, Moderate injuries WSES class II, Severe injuries WSES class III, and WSES class IV. Diagnosis: The diagnostic approach involves a combination of clinical assessment, laboratory investigations, radiological imaging and, in particular situations, surgery. Prompt diagnosis is critical because delays exceeding 24 h are associated with a higher incidence of postoperative complications and a significant rise in mortality. Contrast-enhanced abdominal computed tomography (CT) represents the gold standard for diagnosis in patients who are hemodynamically stable. Management: Duodenal trauma requires a multimodal approach that considers hemodynamic stability, the severity of the injury and the presence of associated lesions. Non-operative management (NOM) is reserved for hemodynamically stable patients with minor duodenal injuries without perforation (AAST I/WSES I), as well as all duodenal hematomas (WSES I–II/AAST I–II) in the absence of associated abdominal organ injuries requiring surgical intervention. All hemodynamically unstable patients, those with peritonitis, or with CT findings consistent with duodenal perforations or AAST grade III or higher injuries are candidates for emergency surgery. If intervention is required, primary repair should be the preferred option whenever feasible, while damage control surgery is the best choice in cases of hemodynamic instability, severe associated injuries, or complex duodenal lesions. Definitive reconstructive surgery should be postponed until the patient has been adequately resuscitated. The role of endoscopic techniques in the treatment of duodenal injuries and their complications is expanding. Conclusions: Duodenal trauma is burdened by potentially high mortality. Among the possible complications, duodenal fistula is the most common, followed by duodenal obstruction, bile duct fistula, abscess, and pancreatitis. The overall mortality rate for duodenal trauma persists to be significant with an average rate of 17%. Future prospective research needed to reduce the risk of complications following duodenal trauma. Full article

The recognition of trauma-induced coagulopathy (TIC) as an endogenous response to traumatic injuries rather than a consequence of therapeutic interventions has shifted the clinical approach toward an early and physiologically based hemostatic resuscitation. Prompt identification and correction of fibrinolysis and fibrinogen level derangements, dysregulated thrombin generation, and platelet dysfunction represent the cornerstones of the treatment strategies. Currently available viscoelastic hemostatic assays (VHAs) are point-of-care devices able to rapidly assess the phases of clot initiation, propagation, stabilization, and degradation, as well as isolate the contribution of specific elements—e.g., fibrinogen—to the coagulation process in fully automated analyses by multi-channel single-use cartridges. As a result, in the last decade, VHAs have been widely investigated as tools to implement individualized protocols of hemostatic resuscitation. Current guidelines support their use to optimize transfusion load in a goal-directed strategy. Nevertheless, contrasting evidence has emerged regarding the improvement in main clinical outcomes induced by the VHA-based algorithm of hemostatic resuscitation compared with those guided by conventional coagulation tests, and their place in the management of this peculiar population is still a matter of debate. We propose a narrative review ranging from TIC physiopathology as a proper substrate for viscoelastic diagnostic technique, through the strengths and weaknesses of VHAs, to their application in clinical practice. Full article

(1) Background: This study aimed to assess the characteristics and factors influencing 72 h survival after traumatic cardiac arrest (TCA), comparing out-of-hospital TCA (oTCA) with in-hospital TCA (iTCA). (2) Methods: This is a retrospective review of 286 patients with TCA admitted to the regional trauma center (RTC) in Gangwon Province, Korea, between 2013 and 2019. (3) Results: Transfer from another hospital (hazard ratio [HR] 0.86 [0.76–0.97]) and longer duration between accident and cardiopulmonary resuscitation (CPR) (HR 0.95 [0.90–0.99]) were associated with lower 72 h mortality. Transfer showed a significant association with lower 72 h mortality in all patients and in the high-injury-severity-score (ISS) group, but not in the low-ISS group. Subgroup analysis indicated that patients transferred from another hospital had significantly lower HR than directly admitted patients to the RTC for oTCA occurrence (HR 0.36 [0.23–0.57]), total CPR duration > 30 min (HR 0.34 [0.23–0.52]), and accident-to-CPR duration < 30 min (HR 0.25 [0.11–0.55]). Additionally, shorter distances from the accident site to the first hospital were associated with lower relative HRs. (4) Conclusions: Considering the extremely poor outcomes of TCA, basic resuscitation and evaluation at nearby medical institutions rather than immediate transfer to specialized trauma centers, particularly when TCA occurs or is anticipated, are important. Early damage-control resuscitation at a nearby hospital can impact on improving the survival rate of patients with TCA. Full article

Background: Classical teaching dictates that damage control resuscitation is ideally implemented within the first or ‘golden’ hour after trauma-related hemorrhage. Given the heterogeneity of trauma, varied models must be utilized to guide ongoing investigation. We sought to determine exactly what happens during the ‘golden hour’ by varying hemorrhage and down times and mimicking venous or arterial bleeding while varying oxygen therapy, a readily available pre-hospital intervention, on survival in a small-animal rodent model. Methods: Rats were bled by 40% of their blood volume over 30 or 60 min, with varied ‘down-times’ of 30, 45, or 60 min. F_iO₂ was administered at 21% or 40%, mimicking nasal cannula. Multiple linear regression was performed between the independent variables and each measured outcome. Sub-group analyses were stratified by survival. Results: There was no statistically significant variation in end-organ insult (lactate), cardiac functioning (cardiac output or left ventricle fractional area of change), mean arterial pressure at end experiment, survival, or survival times among the groups. Conclusions: This study adds to the data against an all-encompassing golden hour, as even a rapid hemorrhage with long down time did not decrease survival. Furthermore, we add to the body of literature in this field by examining cardiac markers of injury with transthoracic echocardiography. Full article

Introduction: Non-compressible torso hemorrhage (NCTH) is a major cause of preventable mortality in trauma, particularly when immediate surgical intervention is not available. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as a promising technique to control severe hemorrhaging and stabilize patients until definitive surgical care can be performed. Case Presentation: We report the case of a 45-year-old woman who sustained multiple traumatic injuries—including thoracic, pelvic, and aortic damage—after a fall from approximately 5 m in an apparent suicide attempt. She arrived at a secondary-level trauma center in profound hemorrhagic shock, unresponsive to standard resuscitation. Interventions: As the patient’s condition deteriorated to cardiac arrest, an emergent REBOA procedure was performed by emergency physicians. This intervention rapidly restored hemodynamic stability, enabling damage control resuscitation and safe transfer to a Level 1 Trauma Center for definitive surgical management, including thoracic endovascular aortic repair and splenectomy. Outcomes: After prolonged intensive care, the patient recovered sufficiently to be discharged for rehabilitation. This case illustrates the life-saving potential of early REBOA deployment in a non-surgical, resource-limited setting to bridge patients to definitive care. Conclusions: This case supports integrating REBOA into emergency trauma protocols, particularly in centers without immediate surgical capabilities. Further research is warranted to refine REBOA deployment strategies, balloon positioning, patient selection, and the role of imaging guidance. Full article

Hemorrhagic shock remains a leading cause of preventable death worldwide, with mortality patterns varying significantly based on injury mechanisms and severity. This comprehensive review examines the complex pathophysiology of hemorrhagic shock, focusing on the temporal evolution of inflammatory responses, biomarker utility, and evidence-based therapeutic interventions. The inflammatory cascade progresses through distinct phases, beginning with tissue injury and endothelial activation, followed by a systemic inflammatory response that can transition to devastating immunosuppression. Recent advances have revealed pattern-specific responses between penetrating and blunt trauma, necessitating tailored therapeutic approaches. While damage control resuscitation principles and balanced blood product administration have improved outcomes, many molecular targeted therapies remain investigational. Current evidence supports early hemorrhage control, appropriate blood product ratios, and time-sensitive interventions like tranexamic acid administration. However, challenges persist in biomarker validation, therapeutic timing, and implementation of personalized treatment strategies. Future directions include developing precision medicine approaches, real-time monitoring systems, and novel therapeutic modalities while addressing practical implementation barriers across different healthcare settings. Success in hemorrhagic shock management increasingly depends on integrating multiple interventions across different time points while maintaining focus on patient-centered outcomes. Full article

Reactive oxygen species (ROS) play an important role in ischemia–reperfusion (I/R) after cardiac arrest and cardiopulmonary resuscitation (CA-CPR). Early administration of vitamin C at a high dose in experimental models resulted in less myocardial damage and had a positive effect on survival after resuscitation. Here, we postulated that the ROS scavenging activity of an anthocyanin (i.e., delphinidin) would positively influence resuscitation outcomes. We hypothesized that administration of delphinidin immediately after CA-CPR could attenuate systemic inflammation in a standardized mouse model and thereby improve survival and long-term outcomes. Outcomes up to 28 days were evaluated in a control group (saline-treated) and a delphinidin-treated cohort. Survival, neurological and cognitive parameters were assessed. Post-CPR infusion of delphinidin deteriorated survival time after a 10 min CA. Survivors amongst the controls showed significantly more anxious behavior than in the pre-CPR phases. This tendency was also observed in the animals treated with delphinidin. In our study, we did not find an improvement in survival with delphinidin after CA-CPR and observed no effect on learning behavior. Our long-term behavioral tests clearly show that CA-CPR is associated with the development of post-interventional anxiety-like symptoms. Our findings open up scopes to investigate the intrinsic factors (e.g., oxidative stress, inflammatory and systemic-microbial response, etc.) influencing the therapeutic efficacy of anthocyanins in vivo. Full article