Efficacy of an Extracorporeal Endotoxin Adsorber System during Hyperdynamic Porcine Endotoxemia

Abstract

Background: Endotoxemia is a crucial factor in the pathogenesis of sepsis. Elimination of endotoxin is aimed at the reduction of sepsis-related morbidity and lethality. The objective of this study was to examine the impact of an endotoxin adsorber on hemodynamics, O₂ exchange and metabolism during resuscitated porcine endotoxemia. Methods: Twenty pigs were randomized into 2 intervention groups (n = 7 each) and 1 control group (n = 6). Endotoxemia was induced by continuous intravenous application of lipopolysaccharide for 8 h. Adsorber therapy was started at the same time as the induction of endotoxemia or 2 h later. An extracorporeal hemoperfusion device using immobilized human serum albumin for endotoxin adsorption was used. Results: Hemodynamic, metabolic and acid-base parameters, as well as the kinetics of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-α, were characteristic for endotoxic shock. Endotoxin plasma levels were low (arterial, hepatic and portal vein). None of the parameters were significantly influenced by the adsorber system. Conclusion: Despite typical clinical signs of endotoxemia, the adsorber system had no significant effect on hemodynamic, metabolic and acid-base parameters during endotoxic shock. The reasons for the absence of an effect are elusive; however, failure of the method per se or exceeded capacity of the adsorber cannot be excluded.

Störungen des angeborenen Immunsystems bei akuten und chronischen Lebererkrankungen

“…The capacity of albumin to bind endotoxin could also be an explanation for the effect seen with MARS therapy [148]. It remains unclear whether it will ever be possible to use this interesting strategy in patients, since preclinical data are not yet convincing [151].…”

Endotoxin elimination in sepsis: physiology and therapeutic application

“…In the only large animal study available so far, Bracht et al [34] examined the impact of an extracorporeal endotoxin adsorber on hemodynamics, O 2 exchange, and metabolism during resuscitated porcine endotoxemia. Pigs were randomized for intravenous continuous application of LPS of E. coli O111:B4 (0.1 μg h −1 kg −1 ) for 8 h or sham.…”

“…It was concluded that despite typical clinical signs of endotoxemia, the adsorber system had no significant effect on hemodynamic, metabolic, and acid-base parameters during endotoxic shock. The reasons for the absence of an effect were elusive; however, failure of the method per se or exceeded capacity of the adsorber could not be excluded [34].…”

A novel polysulfone-based affinity membrane with high hemocompatibility: preparation and endotoxin elimination performance

“…7,8 In this treatment strategy of hemoperfusion, circulating endotoxin and immune mediators in blood are removed by a selective adsorber. [9][10][11][12] The adsorber Toraymyxin was developed by Toray Industries Inc. based on polymyxin B-immobilized polystyrene fabric, and has been applied to sepsis patients as a blood purication medical device in Japan. 13,14 In the late 2000s, over 30 000 patients received Toraymyxin treatment and positive results were achieved.…”