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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While early plasma transfusion for the treatment of patients with ongoing major hemorrhage is widely accepted as part of the standard of care in the hospital setting, logistic constraints have limited its use in the out-of-hospital setting. Freeze-dried plasma (FDP), which can be stored at ambient temperatures, enables early treatment in the out-of-hospital setting. ⋯ We describe the clinical rationale behind the use of FDP at the point-of-injury, the drafting of the administration protocol now being used by Israel Defense Forces advanced life support providers, the process of procurement and distribution, and preliminary data describing the first casualties treated with FDP at the point of injury. It is our hope that others will be able to learn from our experience, thus improving trauma casualty care around the world.
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Lipopolysaccharide (LPS, endotoxin) is a structural component of the gram-negative outer membrane. The lipid A moiety of LPS binds to the LPS receptor complex expressed by leukocytes, endothelial cells, and parenchymal cells and is the primary component of gram-negative bacteria that is recognized by the immune system. Activation of the LPS receptor complex by native lipid A induces robust cytokine production, leukocyte activation, and inflammation, which is beneficial for clearing bacterial infections at the local level but can cause severe systemic inflammation and shock at higher challenge doses. ⋯ As such, monophosphoryl lipid A is currently used as an adjuvant in several human vaccine preparations. Because of the potency of lipid A analogs as immunoadjuvants, numerous laboratories are actively working to identify and develop new lipid A mimetics and to optimize their efficacy and safety. Based on those characteristics, lipid A analogs represent an attractive family of immunomodulators.
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Ischemia-reperfusion injury (IRI) is a common occurrence following myocardial infarction, transplantation, stroke, and trauma that can lead to multiple organ failure, which remains the foremost cause of death in critically ill patients. Current therapeutic strategies for IRI are mainly palliative, and there is an urgent requirement for a therapeutic that could prevent or reverse tissue damage caused by IRI. ⋯ In this review, we highlight the mechanisms involved in neutrophil recruitment, activation, and adherence and how this contributes to disease severity in IRI. Inhibiting neutrophil mobilization, tissue recruitment, and ultimately neutrophil-associated activation of local and systemic inflammatory responses may have therapeutic potential in the amelioration of local and remote tissue damage following IRI.
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Clinical Trial
Activated Protein C Improves Macro and Microvascular Reactivity in Human Severe Sepsis and Septic Shock.
We tested the effects of activated protein C (APC) in macrovascular and microvascular beds within 60 min of treatment. Twelve patients treated with APC for severe sepsis were included. We assessed macrovascular reactivity by phenylephrine arterial dose response. ⋯ Myogenic tone increased (P = 0.03), whereas sympathetic tone decreased (P = 0.03), and myogenic tone was lower than controls before but not after APC treatment. In conclusion, APC improves vascular reactivity both at macrocirculatory and microcirculatory levels very quickly, suggesting that this is not due to protein synthesis or anticoagulant effect. The myogenic properties of vessels could partly drive this effect.
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Comparative Study Observational Study
Diagnostic potential of endotoxin scattering photometry for sepsis and septic shock.
Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. ⋯ Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.