Contributions to nephrology
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Fluid overload may occur in patients with heart failure. Further complications may arise when cardiorenal syndromes develop and the kidneys are unable to eliminate the accumulated fluid. Diuretics represent the fist line of treatment, although in some case they may be ineffective or even dangerous for the patient. ⋯ Then, an evaluation of biomarkers of heart failure and a careful analysis of body fluid composition by bioimpedance vector analysis should be carried out to establish the level of hydration and to guide fluid removal strategies. Last but not least, an adequate extracorporeal technique should be employed to remove excess fluid. Preference should be given to continuous forms of ultrafiltration (slow continuous ultrafiltration, continuous venovenous hemofiltration); these techniques guided by a continuous monitoring of circulating blood volume allow for an adequate restoration of body fluid composition minimizing hemodynamic complications and worsening of renal function especially during episodes of acute decompensated heart failure.
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Comparative Study Controlled Clinical Trial
Efficacy of continuous hemodiafiltration with a cytokine-adsorbing hemofilter in the treatment of acute respiratory distress syndrome.
In the pathophysiology of acute respiratory distress syndrome (ARDS), the increase in capillary and alveolar permeability caused by various humoral mediators and resultant pulmonary interstitial edema play major roles. In this study, the efficacy of continuous hemodiafiltration using a cytokine-adsorbing hemofilter with a membrane made of polymethylmethacrylate (PMMA-CHDF) in the treatment of ARDS patients was investigated. ⋯ Cytokine removal therapy with PMMA-CHDF is expected to be useful as a new therapeutic modality in ARDS patients for non-renal indications.
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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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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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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.