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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Excessive microvascular permeability is a serious complication following hemorrhagic shock and resuscitation (HSR). S1P has been shown to ameliorate microvascular leakage in a model of combined alcohol intoxication and HSR. In the current study, we tested the hypothesis that S1P reduces HSR-induced microvascular leakage by preserving endothelial cell junctional structure and the endothelial glycocalyx through the protection of mitochondrial function. ⋯ S1P treatment during HSR also protects against mitochondrial membrane depolarization. S1P also protects against mitochondrial dysfunction-induced endothelial barrier dysfunction and glycocalyx degradation by acting through mitochondrial complex III. Taken together, our data indicate that S1P protects against HSR-induced mitochondrial dysfunction in endothelial cells, which in turn improves the structure of the endothelial glycocalyx after HSR and allows for better junctional integrity to the prevention of excess microvascular permeability.
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Clinical Trial Observational Study
The Effect of Nutrition on Early Stress-Induced Hyperglycemia, Serum Insulin Levels, and Exogenous Insulin Administration in Critically Ill Patients with Septic Shock: A Prospective Observational Study.
Stress-induced hyperglycemia is common among septic shock patients. Nutritional support influences glucose homeostasis but this effect has never been studied in septic shock. We aimed to determine the course of hyperglycemia and serum insulin levels in critically ill septic shock patients and to address the effects of caloric intake on glycemia, insulin levels, and exogenous insulin requirements. ⋯ In patients with septic shock marked reduced serum insulin levels can be observed during the first 36 h after intensive care unit (ICU) admission that have to be compensated by exogenous insulin administration, a phenomenon gradually improving after 36 h. Feeding is positively associated with exogenous insulin requirements. These results suggest that strategies to manage stress-induced hyperglycemia in patients with septic shock should consider frequent glycemic monitoring, conservative insulin dosing to prevent hypoglycemia when insulin resistance disappears, and slow progressive nutrition support during the early ICU phase as caloric loading may worsen hyperglycemia. This approach may attenuate the risk of glucose variability, hypo- and hyperglycemia and associated poor outcomes.
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Research into potential use of perfluorocarbons for liquid ventilation and as oxygen delivery agents in humans has been underway since the 1960s. While partial liquid ventilation with perfluorocarbons showed promise in animal models and early human investigation, randomized controlled human trials failed to show benefit and an elevated rate of adverse events. Initial approval of Fluosol-DA (Green Cross Corporation, Osaka, Japan) by the United States Food and Drug Administration as an oxygen delivery agent for use in high-risk coronary angioplasty represents the only approved application of these compounds to supplement tissue oxygenation, but the compound was rendered obsolete and removed from the market with the development of advanced angioplasty catheters in the 1990s. ⋯ Early clinical trials of perflubron emulsion in non-cardiac and cardiac surgery were promising, but dose restriction and the requirement for high inspired oxygen concentration to maximize oxygen delivery for prolonged periods of time limited the clinical utility as a replacement for the oxygen carrying capacity of red blood cells. Identification of excess serious adverse events in treated patients resulted in discontinuation of pivotal clinical trials. Continued research investigating different formulations of perfluorocarbons has shown promise in animal studies, but continued research is necessary to prove safety and efficacy in humans.
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Mechanical ventilation is known to activate oxidative stress and proteolytic pathways in the diaphragm. Trauma by inducing inflammation and activating proteolytic pathways may potentiate the effects of mechanical ventilation on the diaphragm. In a blunt chest trauma with concomitant injuries we tested the hypothesis that trauma via inflammation further activates the proteolytic pathways and worsens atrophy in the diaphragm. ⋯ Trauma and mechanical ventilation induced proteolysis and atrophy in the diaphragm, but only polytrauma induced an inflammatory response in the diaphragm. The additional traumatic inflammatory stimulus did not increase the levels of the prementioned variables. These data underline that inflammation is not a major contributor to ventilator-induced diaphragmatic dysfunction.
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Clinical Trial Observational Study
Delta Neutrophil Index for the Prediction of the Development of Sepsis-Induced Acute Kidney Injury in the Emergency Department.
The early prediction of acute kidney injury (AKI) in sepsis and provision of timely treatment may improve outcomes. We investigated the efficacy of the delta neutrophil index (DNI)-which reflects the fraction of immature granulocytes-in predicting sepsis-induced AKI and 30-day mortality in cases of severe sepsis or septic shock. ⋯ Higher DNI values are independent predictors of severe AKI development and 30-day mortality in sepsis. Physicians can use the DNI to quickly determine the severity of sepsis and initial treatment strategies without additional costs and effort.