Contributions to nephrology
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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.
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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.
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Acute lung injury (ALI) and acute kidney injury (AKI) are complications often encountered in the setting of critical illness. Both forms of end-organ injury commonly occur in similar settings of systemic inflammatory response syndrome, shock, and evolving multiple organ dysfunction. Distant organ effects of apparently isolated injuries to the lungs, gut, and kidneys have all been discovered in recent years. In this review of the emerging evidence of deleterious bidirectional organ crosstalk between the lungs and kidney, we will focus on the role of ventilator-induced kidney injury in the pathogenesis of AKI in patients with ALI.
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Review Case Reports
Diuretic therapy in fluid-overloaded and heart failure patients.
Diuretics are the most commonly used drugs to treat clinically diagnosed fluid overload in patients with heart failure. There is no conclusive evidence that they alter major outcomes such as survival to hospital discharge or time in hospital compared to other therapies. However, they demonstrably achieve fluid removal in the majority of patients, restore dry body weight, improve the breathlessness of pulmonary edema and are unlikely to be subjected to a large double-blind randomized controlled trial in this setting because of lack of equipoise. ⋯ Such therapy often requires more intensive monitoring than available in medical wards. If diuretic therapy fails to achieve its clinical goals, ultrafiltration by semipermeable membranes is reliably effective in achieving targeted fluid removal. The combination of diuretic therapy and/or ultrafiltration can achieve volume control in essentially all patients with heart failure.