New Targets for Extracorporeal Blood Purification Therapies in Sepsis

Abstract

As highlighted by the last international consensus definition for sepsis and septic shock (sepsis-3), sepsis comes from a complex relationship between a pathogen and a dysregulated host response. To date, the treatment of sepsis is based on antimicrobial treatment, source control, and organ support. Extracorporeal blood purification therapies have been proposed as adjuvant therapies to modulate the dysregulated inflammatory response. These therapies aim mostly at removing inflammatory mediators (cytokines) and endotoxins from the blood. However, so far, they failed to clearly demonstrate an improvement in patient survival when evaluated in randomized trials. Recently, new devices directly targeting the primary determinants of sepsis, e.g., the pathogen itself and the host immune cells, have been developed. This short review aimed at presenting new blood purification devices that have recently been developed to target pathogens and immune cells. For each, we will present the mechanism of action of the therapy and discuss the related literature.

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses

“…It has been well established that endotoxins are major inflammatory mediators that trigger the release of both proinflammatory and anti-inflammatory cytokines and organ injury in critically ill patients, especially those with sepsis, during the past two decades [ 2 – 4 ]. Accordingly, endotoxins and cytokines are widely recognized as the main therapeutic targets during extracorporeal blood purification (EBP) sessions for the immunomodulation of critical illnesses [ 4 , 5 ]. Currently, EBP uses a series of hemofilters to remove hydrophilic or hydrophobic solutes through the mechanism of convection, diffusion or adsorption, and the solute removal spectrum of a hemofilter is significantly dependent on its own membrane/adsorbent structure and treatment dose [ 6 ].…”

“…Multiple hemofilters, such as Toraymyxin hemofilter (Toray Industries, Tokyo, Japan), the CytoSorb hemofilter (CytoSorbents Corporation, New Jersey, USA) and the oXiris hemofilter (Baxter, Meyzieu, France), have been used to treat critically ill patients in current clinical practice aiming to eliminate endotoxins and/or cytokines despite the lack of solid evidence of survival benefit [ 3 , 7 ]. The failure of EBP therapies to improve survival in these patients could be attributed to the inadequate timing for treatment initiation, inadequate patient selection, inadequate therapeutic target selection and insufficient clearance of inflammatory mediators [ 3 , 5 ]. Instead of the removal of cytokines that are downstream mediators in the immune cascade, the elimination of upstream proinflammatory mediators, such as the pathogen, activated host immune cells and especially damage-associated molecular patterns (DAMPs), could be more suitable therapeutic targets for EBP therapies in the early phase of critical illnesses.…”

Extracorporeal therapy in the treatment of sepsis: In vitro assessment of the effect of an absorbent cartridge on the circulating bacterial concentration and its interaction with the antibiotic therapy

“…The most common devices for EBP when it comes to filters and cartridges are: the Seraph ® 100 Microbind ® Affinity Blood Filter (ExThera Medical, Martinez, CA, USA), a hemoperfusion treatment utilizing heparin to adsorb bacteria, the GARNET ® Hemofilter (BOATM Biomedical, Cambridge, MA, USA), a hemofilter containing hollow polysulfone fibers subsequently coated with a genetically engineered recombinant protein derived from the mannose-binding lectin, and finally, the Hemopurifier ® (Aethlon Medical, San Diego, CA, USA) that combines plasmapheresis and an adsorption mechanism in order to separate pathogens from the blood. 6 Within different extracorporeal therapies recently surfaced, the techniques which take advantage of adsorption have raised interest, underlining the potential utility and effectiveness of applying these therapies in septic patients.…”

Analysis of risk factors for death in 59 cases of critically ill neonates receiving continuous renal replacement therapy-a two-center retrospective study

“…For example, it is unnecessary to remove the downstream cytokines but rather the critical factors such as pathogens or speci c host immune cells. These factors are potential targets for extracorporeal blood puri cation therapy for sepsis and require further study [22] .…”