Contributions to nephrology
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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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Different definitions for acute kidney injury (AKI) once posed an important impediment to research. The RIFLE consensus classification was the first universally accepted definition for AKI, and has facilitated a much better understanding of the epidemiology of this condition. The RIFLE classification was adapted by a broad platform of world societies, the Acute Kidney Injury Network group, as the preferred AKI diagnostic and staging system. ⋯ Renal replacement therapy is necessary in approximately 2% of this cohort. AKI that occurs within a 7-day period after cardiac surgery is related to perioperative risk factors, such as preexisting chronic kidney disease, acute ischemia, aorta cross-clamping, or use of cardiopulmonary bypass. AKI that occurs after the first week is mostly a consequence of sepsis or heart failure.
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Sepsis is one of the main causes of death in critically ill patients. The pathophysiology of sepsis is complex and not completely understood. The proinflammatory and anti-inflammatory response leads to cell and organ dysfunction and, in many cases, death. ⋯ Preliminary data indicate the feasibility of these modified techniques in sepsis. Their impact on patient prognosis, however, still needs proof by large randomized clinical trials. Finally, the emerging paradigm of sepsis-induced immune suppression provides additional rationale for the development of extracorporeal blood purification therapy for sepsis.
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We evaluated the ability of the endotoxin activity (EA) assay to determine the need for early intervention for endotoxemia using polymyxin B-based hemoperfusion (PMX-DHP) on septic patients. ⋯ The EA assay can identify patients eligible for PMX-DHP treatment and aids its therapeutic dosing.