Coupled Plasma Filtration Adsorption: Rationale, Technical Development and Early Clinical Experience

Abstract

The adjuvant treatment of sepsis remains a major therapeutic challenge. Blood purification is theoretically appealing if the humoral theory of sepsis is accepted as the basis for intervention. In this setting, blood purification would provide a broad-based restoration of humoral homeostasis thereby avoiding both excessive inflammation and counterinflammation. Several techniques of blood purification have been tried or are under active investigation. One of these is the so-called coupled plasma filtration adsorption (CPFA). CPFA is a novel extracorporeal blood purification therapy aimed at nonselectively reducing the circulating levels and activities of both pro- and anti-inflammatory mediators during sepsis and multiorgan failure. In vitro studies have shown CPFA to be effective in binding a broad range of such mediators proving its technical efficacy. Subsequent animal models have shown a beneficial effect on survival in endotoxemia. These studies have provided the necessary technical developments and biologic rationale for initial human studies. Two phase I/IIa clinical studies have now been performed. Both studies have shown that CPFA improves blood pressure and restores immune function in patients with severe sepsis and multiorgan dysfunction. In this article, we will discuss some of the basic principles involved in sorbent technology, and how these may contribute to treatment efficacy, review animal experiments with CPFA and finally discuss the results of recent human studies and their implications.

Clinical Utility of Extracorporeal Cytokine Hemoadsorption Therapy: A Literature Review

“…An increased understanding of the cell signaling pathways involved in sepsis has led to research efforts focused on reducing systemic cytokine levels by using extracorporeal blood purification [41]. In fact, extracorporeal filtration techniques such as coupled plasma filtration adsorption have shown promise as a potential adjuvant therapy in sepsis and septic shock [41][42][43].…”

Adsorptive Modulation of Inflammatory Mediators Dampens Endothelial Cell Activation

“…Similar beads have been used in pilot studies to modulate concentrations of inflammatory mediators in sepsis patients [13,21,22,23]. To increase their biocompatibility, PS-DVB beads were coated by incubation with albumin solutions of decreasing concentration to yield adsorbents 1–4.…”

New Insights Regarding Rationale, Therapeutic Target and Dose of Hemofiltration and Hybrid Therapies in Septic Acute Kidney Injury

“…Only target molecules within a relatively strict range of molecular weights are adsorbed and treated blood is returned to the patient. Indeed, CPFA improves blood pressure and restores immune function in patients with severe sepsis and multi-organ dysfunction but failed so far to improve survival in large randomized studies [63]. Regarding CCHF in an animal model of septic shock, CCHF was superior to HVHF regarding hemodynamics.…”