Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Corticosteroids have been shown to reduce short-term mortality during septic shock and therefore recommended in the most severe patients as adjuvant therapy. Until recently, recombinant human activated protein C (APC) was also considered in the management of more severe cases. As myocardial depression has long been recognized as a manifestation of organ dysfunction during septic shock, we examined whether corticosteroids (dexamethasone, 150 µg/kg per hour) and/or APC (33 µg/kg per hour) treatments improve sepsis-induced cardiac dysfunction during cecal ligature and puncture-induced septic shock in Wistar rats. ⋯ Cecal ligature and puncture induced hypotension, depression of myocardial systolic performance (demonstrated by significant decreases in dP/dtmax [first derivative of maximal developed pressure during isovolumetric contraction], end-systolic pressure-volume relationship, and preload recruitable stroke work) and alteration of diastolic function (dP/dtmin [first derivative of minimal developed pressure during isovolumetric relaxation]), whereas dexamethasone, APC, and their combination thereof allowed correction of hemodynamic disorders and improved myocardial mechanical efficiency. Cecal ligature and puncture was associated with higher levels of nitric oxide and superoxide anion (O2) in heart (electron paramagnetic resonance studies) and consequently peroxynitrite. Dexamethasone and APC also improved cardiac dysfunction by downregulating the inducible nitric oxide synthase pathway and reducing myocardial oxidative stress.
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Trauma remains the leading cause of morbidity and mortality in the United States among children aged 1 to 21 years. The most common cause of lethality in pediatric trauma is traumatic brain injury. Early coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumatic brain injury. ⋯ Whether this new mechanism of posttraumatic coagulopathy plays a role in children is still unknown. The goal of this review is to summarize the current knowledge on the incidence and potential mechanisms of coagulopathy after pediatric trauma and the role of rapid diagnostic tests for early identification of coagulopathy. Finally, we discuss different options for treating coagulopathy after severe pediatric trauma.
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Observational Study
Elevated Tissue Plasminogen Activator and Reduced Plasminogen Activator Inhibitor Promote Hyperfibrinolysis in Trauma Patients.
Severe hyperfibrinolysis after trauma is a poorly understood phenomenon associated with profound shock, serious anatomic injuries, increased transfusions, and high mortality rates. Molecular mechanisms driving hyperfibrinolysis in trauma have not been completely delineated. The authors aimed to determine the relationship between severe hyperfibrinolysis and outcomes in trauma patients and characterize the role of the plasminogen activator (PA) system in this condition. ⋯ Patients with both elevated tPA and reduced PAI-1 were more severely injured, received more transfusions, and experienced fewer ventilator and hospital-free days. In conclusion, Severe hyperfibrinolysis is observed in a small percentage of trauma patients and is associated with severe injuries, greater transfusions, and worse outcomes. This condition is mediated, in part, by excessive upregulation of profibrinolytic tPA in the absence of concomitant increases in antifibrinolytic PAI-1.
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Neutrophil extracellular traps (NETs), which consist of neutrophil DNA and cytoplasmic proteins, have been shown to be involved in various infectious, inflammatory, and autoimmune diseases. Neutrophil extracellular traps are abundant at the site of infection and acute inflammation. ⋯ Neutrophil extracellular traps are believed to modulate the inflammatory and immune responses of individuals after injury. In this review, the role of NETs in injury, including traumatic injury, ischemia-reperfusion-induced injury, and sepsis, as well as the potential markers and therapeutic targets of NET-related injury will be discussed.
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Observational Study
Oxygen Challenge Test in Septic Shock Patients: Prognostic Value and Influence of Respiratory Status.
Transcutaneous oxygen pressure (PtcO2) value in response to an increase of FiO2 or oxygen challenge test (OCT) in ventilated patients has been reported to be related to peripheral perfusion and outcome during septic shock. However, patients with sepsis-related acute respiratory distress syndrome could demonstrate compromised arterial oxygenation with OCT impairment decoupled to circulatory failure. The aims of this study were to confirm the prognostic value of OCT and to explore the influence of respiratory status on OCT results. ⋯ Moreover, patients with low OCT results at T24 exhibited more severe respiratory failure (P < 0.01). The OCT at T24 is related to outcome but is influenced by the severity of respiratory failure. Our results suggest considering with caution hemodynamic management based on OCT in septic shock patients with altered pulmonary function.