Contributions to nephrology
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Since 1994, a polystyrene fiber cartridge used for extracorporeal hemoperfusion, to which polymyxin B is bound and immobilized, has been used in septic patients in order to absorb and remove circulating lipopolysaccharide, thereby neutralizing the effects of this endotoxin. This therapy gradually gained acceptance as the amount of evidence increased from initial small clinical studies to a carefully conducted systematic review, and ultimately to the multicentered randomized clinical trial conducted in Italy, entitled the EUPHAS Study (Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock). While the conclusions of this initial randomized controlled trial were in agreement with previous studies, it possessed some important limitations, including a slow accrual rate, enrolling only 64 patients between 2004 and 2007, inability to blind treating physicians, and a premature study termination based on the results of the scheduled interim analysis. ⋯ In response, Italian investigators and users of this treatment have designed a new prospective multicentered, collaborative data collection study, entitled EUPHAS 2. The aim of the EUPHAS 2 project is to collect a large database regarding polymyxin B-hemoperfusion treatments in order to better evaluate the efficacy and biological significance of endotoxin removal in clinical practice. Additionally, this study aims to verify the reproducibility of the data currently available in the literature, evaluate the patient population chosen for treatment and identify subpopulations of patients who may benefit from this treatment more than others.
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Sepsis is one of the main causes of death in critically ill patients. The pathophysiology of sepsis is complex and not completely understood. The proinflammatory and anti-inflammatory response leads to cell and organ dysfunction and, in many cases, death. ⋯ Preliminary data indicate the feasibility of these modified techniques in sepsis. Their impact on patient prognosis, however, still needs proof by large randomized clinical trials. Finally, the emerging paradigm of sepsis-induced immune suppression provides additional rationale for the development of extracorporeal blood purification therapy for sepsis.
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We evaluated the ability of the endotoxin activity (EA) assay to determine the need for early intervention for endotoxemia using polymyxin B-based hemoperfusion (PMX-DHP) on septic patients. ⋯ The EA assay can identify patients eligible for PMX-DHP treatment and aids its therapeutic dosing.
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The care of acute kidney injury (AKI) in critically ill children shares several features with adult AKI with some critical distinctions: in both settings, however, the exact identification of renal dysfunction, in-depth knowledge of disparate risk factors and patient-specific management are the primary targets in order to provide optimal care. This article will specifically review recent work published on pediatric AKI about definition and epidemiology, the possible etiologies in specific conditions, and the newest laboratory investigations necessary to diagnose AKI severity. A short description of pediatric renal replacement therapies and their potential application to extracorporeal membrane oxygenation will also be described.
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There is a large amount of support for the safety of polymyxin-B (PMX-B) hemoperfusion in the treatment of septic shock from Japan and Europe. There is also support for potential efficacy, although randomized controlled trials are few and conflicting. ⋯ The variability in the number of treatment cartridges used, the selection of subjects based on likelihood of endotoxin presence without endotoxin measurement, and small sample sizes in mainly single-center trials have also been cited. The newly designed EUPHRATES trial (Evaluating Use of Polymyxin Hemoperfusion in a Randomized Controlled Trial of Adults treated for Endotoxemia and Septic Shock) addresses many of the methodological issues and represents a significant opportunity to test for clinical efficacy of endotoxin removal in the critically ill septic patient.