Background & Reviews

Sepsis is a well-recognized worldwide healthcare issue, ultimately resulting in significant mortality, morbidity and resource utilization. In its most severe form, sepsis causes multi-organ dysfunction. Sepsis induces the activation of complement factor and the release of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β), resulting in a systemic inflammatory response. Several clinical and experimental studies have reported that treatment using adsorption of cytokines is beneficial during endotoxemia and sepsis. This review article analyzes the efficacy of CytoSorb adsorber in reducing the inflammatory response during sepsis. The CytoSorb adsorber is known to have excellent adsorption rates for inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, and TNF-α. Studies have demonstrated that treatment with cytokine adsorbing columns has beneficial effects on the survival rate and inflammatory responses in animal septic models. Several cases have been reported in which treatment with cytokine adsorbing columns is very effective in the stabilization of organ failure and hemodynamics in critically ill patients. Therefore, treatment with cytokine adsorbing columns may play an important role in the treatment of sepsis in the near future.

This review outlines the use of extracorporeal therapies in the treatment of sepsis and septic AKI, considering the classic aspects of extracorporeal renal replacement therapy including indications, timing, and delivered dose but also discussing the various techniques that are currently used to achieve immune homeostasis. The authors further discuss the evidence accumulated to date and suggest possibilities for the future treatment of this entity of patients. In this context, the CytoSorb therapy is mentioned as one of the most promising approaches, due to its improved biocompatibility and therefore the opportunity for whole blood perfusion, its efficiency in removing multiple inflammatory mediators shown in animals studies as well as in case reports and due to its beneficial effects on chemokine gradients, which may restore chemokine gradients towards infected tissue and away from healthy organs through leukocyte trafficking control.

This review gives a good overview on the effects of blood purification therapies at the immunologic and cellular level. It is discussed how therapies like high-volume hemofiltration, hemoadsorption, coupled plasma filtration adsorption and high-cut off membranes have been improved in the meantime and adapted to the “setting” of sepsis.

Since continuous renal replacement therapy (CRRT) in the treatment of sepsis and systemic inflammation response syndrome (SIRS) showed relatively negative results, attention is now drawn to new membranes and sorbents that could better eliminate massive amounts of unbound mediators in wider spectrum and also in greater magnitude.
This review summarizes the use and evidence of these newly designed technologies i.e. high cutoff CRRT membranes, high non-selective adsorptive CRRT membranes, high selective adsorptive CRRT membranes and cytokine-adsorbing columns.
The authors state, that “CytoSorb might be seen as the most promising although not having the ability to fix endotoxin”.

In this article the authors discuss the new “cytokinic” approach introduced by Namas et al. potentially explaining the mode of action of hemoadsorption using large surface-area polymer (i.e. CytoSorb) compared to the hitherto propagated “cytotoxic” hypotheses.

This review discusses the use of available technologies for extracorporeal blood purification (hemoadsorption, coupled plasma filtration adsorption, high cut-off- and hemofiltration membranes) in sepsis. The authors specifically address the medical/scientific evidence of CytoSorb, but also of all other procedures.

This review informs about the latest advances in blood purification for sepsis and how they relate to current concepts of disease. The authors further review the underlying mechanisms and the current medical/scientific evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration and high-cutoff hemofiltration/hemodialysis. Though all technologies are biocompatible and effective (reduction of cytokines and in part bacterial toxines, improvement of physiological parameters like hemodynamics and oxygenation), there is an urgent need for confirming large multicenter trials evaluating the ability of these therapies to improve clinical outcomes. Regarding CytoSorb, the authors mainly discuss the two Kellum in vivo studies (endotoxin and cecal ligation and puncture model).

In this article the authors provide a concise overview of selected extracorporeal modalities (influencing the circulating levels of inflammatory mediators like cytokines and chemokines etc.) currently in clinical use (hemofiltration-, adsorption- and cell-based therapies). They also briefly introduce some new promising techniques for sepsis.
CytoSorb is discussed to effectively reduce cytokine levels mainly focussing on the Kellum in vivo study using the cecal ligation and puncture rat model.

This review gives a good overview on the effects of blood purification therapies at the immunologic and cellular level. It is discussed how therapies like high-volume hemofiltration, hemoadsorption, coupled plasma filtration adsorption and high-cut off membranes have been improved in the meantime and adapted to the “setting” of sepsis.

This review discusses the various modalities of extracorporeal blood purification, the existing evidence and future prospects.
Regarding CytoSorb, the authors briefly refer to the known advantages (reduction of cytokine levels, improvement of hemodynamics and survival).