Contributions to nephrology
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Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative-induced abdominal sepsis is likely to be associated with high circulating endotoxin. In June 2009, the EUPHAS study (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis) was published in JAMA. ⋯ The PaO(2)/FiO(2) ratio increased slightly (235 to 264; p = 0.049) in the polymyxin B group, but not in the conventional therapy group (217 to 228; p = 0.79). SOFA scores improved in the polymyxin B group, but not in the conventional therapy group (change in SOFA: -3.4 vs. -0.1; p = 0.001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional therapy group (unadjusted HR: 0.43, 95% CI: 0.20-0.94; adjusted HR: 0.36, 95% CI:0.16-0.80). The study demonstrated how polymyxin B hemoperfusion added to conventional therapy significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality in a targeted population with severe sepsis and/or septic shock from intra-abdominal Gram-negative infections.
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Continuous renal replacement therapy (CRRT) has been extensively used in Japan as renal support for critically ill patients managed in the ICU. In Japan, active research has also been conducted on non-renal indications for CRRT, i.e. the use of CRRT for purposes other than renal support. Various methods of blood purification have been attempted to remove inflammatory mediators, such as cytokines, in patients with severe sepsis or septic shock. ⋯ In evaluating the efficacy of CRRT for non-renal indications, it is essential to focus on patients subjected to be studied, such as severe sepsis or septic shock, and to evaluate its indication, commencement, termination of therapy and also its therapeutic effects based on analysis of blood levels of the target substances to be removed (e.g. cytokines). IL-6 blood level appears to be useful as a variable for this evaluation. It is expected that evidence endorsing the validity of these methods now being attempted in Japan will be reported near future.
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Acute kidney injury (AKI) is a common complication of critical illness. While the etiology of AKI in critically ill patients is likely often multifactorial, sepsis has consistently been found an important contributing factor and has been associated with high attributable morbidity and mortality. Accordingly, the timely identification of septic AKI in critically ill patients is clearly a clinical priority. ⋯ In addition, several urinary biochemical tests, derived indices and microscopy have also been widely cited as valuable in the diagnosis and classification of AKI. However, the value of these urinary tests in the diagnosis, classification, prognosis and clinical management in septic AKI remains unclear, due in part to a lack of kidney morphologic changes and histopathology in human studies of septic AKI. This review will summarize the urinary biochemistry and microscopy in septic AKI.
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Dysnatremias (hypo- and hypernatremia) are common in patients admitted to the intensive care unit (ICU) with a prevalence approaching 20-30% in some studies. Recent data reveals that both hypo- and hypernatremia present on admission to or developing in the ICU are independent risk factors for poor prognosis. The origin of hypernatremia in the ICU is often iatrogenic and due to inadequate free water replacement of ongoing water losses. ⋯ The appropriate use of hypertonic (3%) saline in the treatment of hyponatremic encephalopathy has also shown to be very effective and the use of this therapy is reviewed here. Vasopressin receptor antagonists have also been shown to be effective at increasing serum sodium levels in patients with either euvolemic or hypervolemic hyponatremia and represent another therapeutic option. Recent data demonstrates that proper correction of hyponatremia is associated with improved short- and long-term outcomes.
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Endotoxin removal by polymyxin B immobilized cartridge inactivates circulating proapoptotic factors.
Severe sepsis and septic shock continue to be major clinical challenges due to high associated mortality. Lipopolysaccharide (LPS) is a component of the cell membrane of Gram-negative bacteria, and is believed to initiate septic-induced signaling, inflammation and organ damage, including acute renal failure. Polymyxin B (PMX-B) hemoperfusion of septic patients can improve survival and decreasing organ dysfunction by removing circulating LPS. Unfortunately, some clinicians have been slow to adopt this novel therapy due to the lack of understanding of the cellular mechanisms involved in this treatment. Apoptosis, or programmed cell death, is known to contribute to acute renal failure and overall organ dysfunction during sepsis, and can be activated by LPS-initiated signaling pathways. Therefore, the protective renal effects associated with PMX-B hemoperfusion of septic patients may result from alterations in cellular apoptosis. This chapter will review recent data regarding the role of apoptosis prevention in the mechanism leading to the improved outcome and decreased acute renal failure associated with PMX-B hemoperfusion during sepsis. ⋯ The protective effects of extracorporeal therapy with PMX-B on the development of acute renal failure result, in part, through its ability to reduce the systemic proapoptotic activity of septic patients on renal cells.