Contributions to nephrology
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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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Endotoxin, which consists of lipopolysaccharide (LPS), is an outer membrane component of the Gram-negative bacterial cell wall. Endotoxin in the blood stream from an infectious focus or through translocation from the gut plays an important role in the pathogenesis of severe sepsis and septic shock. It binds to monocytes and macrophages, activating them to trigger the production of a variety of mediators. ⋯ In Japan, PMX has been clinically used since 1994under the national health insurance system. It is estimated that over 80,000 patients have received PMX treatment in Japan. Not only has PMX been clinically used safely in Japan, but also in other countries.
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Endotoxin activity (EA) plays an essential role in sepsis syndrome pathogenesis. There has been considerable interest in measuring and removing EA to predict and improve the morbidity and mortality of patients with sepsis. We performed a prospective study to assess the prevalence of EA in critically ill patients and its association with organ dysfunction and outcome, as well as in septic shock. ⋯ Our study demonstrated that EA level is independent from the type or the source of infection, but reflects the severity of illness in critically ill septic shock patients. Extracorporeal EA removal (PMX-HP) was assessed following our ICU clinical practice. PMX-HP seems to have better outcome, but further studies are required to verify this hypothesis.
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The extracorporeal carbon dioxide removal (ECCO(2)R) concept, used as an integrated tool with conventional ventilation, plays a role in adjusting respiratory acidosis consequent to tidal volume (Vt) reduction in a protective ventilation setting. This concept arises from the extracorporeal membrane oxygenation (ECMO) experience. Kolobow and Gattinoni were the first to introduce extracorporeal support, with the intent to separate carbon dioxide removal from oxygen uptake; they hypothesized that to allow the lung to 'rest' oxygenation via mechanical ventilation could be dissociated from decarboxylation via extracorporeal carbon dioxide removal. ⋯ The future development of more and more efficient devices capable of removing a substantial amount of carbon dioxide production (30-100%) with blood flows of 250-500 ml/min is foreseeable. Moreover, in the future ARDS management should include a minimally invasive ECCO(2)R circuit associated with noninvasive ventilation. This would embody the modern mechanical ventilation philosophy: avoid tracheal tubes; minimize sedation, and prevent ventilator-induced acute lung injury and nosocomial infections.
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Several large observational studies or randomized controlled trials in the field of critical care nephrology have been completed and reported, or recently completed or have recently begun recruitment. These studies provide important information to guide our appreciation of current practice and consider new potentially effective intervention for the prevention or attenuation of acute kidney injury or suggest new avenues for the use of renal replacement therapy (RRT) in the treatment of sepsis. In particular, two studies, the ATN study and the RENAL study (both multicenter randomized controlled trials of > 1,000 patients) provide, for the first time, level I evidence to guide the practice of RRT in critically ill patients and to better define the optimal intensity of such RRT in this setting. Clinicians practicing in the field of critical care nephrology need to be aware of these trials, their details, their findings or design or current recruitment rate and likely time of completion to continue to offer their patients the highest level of evidence-based medical care.