Immunomodulation in Sepsis: The Role of Endotoxin Removal by Polymyxin B-Immobilized Cartridge

Abstract

Severe sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Endotoxin is a component of gram-negative bacteria and plays an important role in the pathogenesis of septic shock when it is recognized by immune cells. Removal of endotoxin could be an effective adjunctive approach to the management of sepsis. Devices to adsorb endotoxin or inflammatory cytokines have been designed as a strategy to treat severe sepsis, especially sepsis caused by gram-negative bacteria. Polymyxin B-immobilized cartridge has been successfully used to treat patients with sepsis of abdominal origin. Although this cartridge was conceived to adsorb endotoxin, several other immunological mechanisms have been elucidated, and this device has also yielded promising results in patients with nonseptic respiratory failure. In this paper, we summarize the immune modulation actions of Polymyxin B-immobilized cartridge to explore its potential usefulness beyond endotoxin elimination.

Blood purification in intensive care patients with multiple organ dysfunction syndrome and sepsis after cardiac surgery

“…Bakulev NSPCCS in 2009-2016, showed the safety and efficacy of the combined therapies mentioned above. [53,54] We observed that the combination of LPS-adsorption and HDF filters with high cut-off EMiC2 membranes led to a 34% MAP increase [from 76 (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81) to 90 (85-102) mmHg, P < 0.001] with reduced vasopressor and inotropic support. The increase in MAP during LPS-adsorption with CPFA was 12% with the significant decrease in vasopressor support [the dose of noradrenaline was halved from 0.2 (0.15-0.3) to 0.1 (0.05-0.15) µg/kg/min, P = 0.024].…”

“…[64][65][66][67] LPS-adsorption using Toraymyxin-PMX-20R Polymyxin B immobilized fiber cartridges was found to be effective, simultaneously acting through sorption and apheresis on bacterial endotoxin, systemic inflammatory mediators and activated immune cells. [59][60][61]68,69] CPFA performs an immunomodulatory role by acting on inflammatory mediators (interleukin-1β, -6, -8, -10, -18, tumor necrosis factor-α and others) via various mass transfer mechanisms such as diffusion, convection and adsorption. The advantages of CPFA include the passage of plasma (and not blood) through the sorption column, which increases the contact time with the sorption surface and improves the efficiency of the procedure.…”

A Pilot Study of Selective Lipopolysaccharide Adsorption and Coupled Plasma Filtration and Adsorption in Adult Patients with Severe Sepsis

“…Discussing the possibility of immunomodulation during selective LPS adsorption, some researchers explain immunomodulation by direct endotoxin elimination (mediated mechanism) [30]. Other researchers are of the opinion that circulating cytokines and growth factors are removed directly, as they present in the eluate from used PMX cartridge fibres after the procedure [31].…”

Interleukin-6 in cardiac surgery

“…Extracorporeal support systems may serve as cytokine removal facilities (44). Polymyxin B-immobilized cartridge has been successfully used in endotoxin elimination (49). CytoSorb® is effective in reducing postoperative systemic inflammatory response syndrome.…”