Contributions to nephrology
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Clinical Trial
Continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter for severe acute pancreatitis.
It has been reported that hypercytokinemia plays a pivotal role in the pathophysiology of severe acute pancreatitis (SAP). In our previous reports, continuous hemodiafiltration (CHDF) using a polymethyl methacrylate (PMMA) membrane hemofilter (PMMA-CHDF) was found to be capable of efficiently removing various cytokines from circulating blood. The present study was undertaken to evaluate the efficacy of PMMA-CHDF aimed at cytokine removal in the treatment of SAP. ⋯ At the time of weaning from PMMA-CHDF, blood IL-6 level had decreased to 99 pg/ml. The mortality rate among patients who received PMMA-CHDF was 6.1%, and significantly lower than that of patients before the introduction of PMMA-CHDF under non-renal indication (25.0%). These findings suggest that PMMA-CHDF is effective for treatment of SAP and that it can be expected to contribute to improving the outcome of SAP patients.
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Sepsis involves a complex interaction between bacterial toxins and the host immune system. Endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis producing proinflammatory cytokines and activating the complement system, and is thus an ideal potential therapeutic target. Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-F) has been shown to bind and neutralize endotoxin in both in vitro and in vivo studies. ⋯ In this study, PMX-F, when added to conventional therapy, significantly improved hemodynamics and organ dysfunction, and reduced 28-day mortality in this targeted population. There is clear biological rationale for endotoxin removal in the clinical management of severe sepsis and septic shock. The current literature seems to provide some support for this premise, and provides the basis for further rigorous study.
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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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During critical illness, reductions in renal blood flow (RBF) are believed to be a major cause of kidney dysfunction, and therapy is often aimed at restoration of RBF. Despite this, our ability to measure RBF during critical illness has been limited by the invasiveness of the available techniques. Ciné Phase-Contrast Magnetic Resonance Imaging (CPC-MRI) represents an entirely noninvasive, contrast-free method of measuring blood flow with the potential of enabling the measurement of blood flow to major organs including the kidney. We have recently assessed the feasibility of measuring RBF by means of CPC-MRI in 2 critically ill patients with septic acute kidney injury and were able to compare such measurements to those obtained in a normal volunteer.
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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.