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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Randomized Controlled Trial Multicenter Study
Incidence, Patient Characteristics, Mode of Drug Delivery, and Outcomes of Septic Shock Patients Treated with Vasopressors in the Arise Trial.
To describe the utilization of vasopressors (VP) in patients enrolled in the Australasian Resuscitation In Sepsis Evaluation (ARISE) trial, and to explore the association between time to VP and 90-day mortality. ⋯ 50% of the ARISE cohort commenced VP within 4.4 h of ED presentation, and many did so prior to central venous access. Earlier initiation of VP was associated with greater crude and adjusted 90-day mortality.
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Several adverse events have been associated with the infusion of hemoglobin-based oxygen carriers (HBOCs), including transient hypertension, gastrointestinal, pancreatic/liver enzyme elevation, and cardiac/renal injury in humans. Although several mechanisms have been suggested, the basis of HBOC toxicity is still poorly understood. Scavenging of vascular endothelial nitric oxide (NO) and heme-mediated oxidative side reactions are thought to be the major causes of toxicity. ⋯ HBOCs display a diversity of physicochemical properties, including molecular size/cross-linking characteristics leading to differences in oxygen affinity, allosteric, redox properties, and even oxidative inactivation by protein/heme clearing mechanisms. These diverse characteristics can therefore be manipulated independently, leaving open the possibility of engineering a safe and effective HBOC. To date, several antioxidative strategies have been proposed to counteract the redox side reactions of current generation HBOCs.
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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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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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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.