Septic shock has a high mortality risk despite the availability of various treatments. Endotoxin, that is present in the cell walls of gram-negative bacteria, is a potent trigger of innate immunity. Endotoxin leads to an activation of a cascade with an overwhelming systemic overflow of pro- and anti- inflammatory mediators at the early phase of sepsis with generalized vascular endothelial damage, tissue injury and multi-organ failure.

Extracorporeal blood purification therapies aim to reduce the circulating level of endotoxin. Different extracorporeal blood purification systems are available. The oXiris™ device comprises a surface treated AN69 membrane capable to adsorb a large spectrum of plasma cytokines, such as IL-6 and HMGB1 protein. The positively charged inner surface of the membrane allows absorbing negatively charged bacterial products such as endotoxin. From an historical perspective, filters containing AN69-based membranes have been the most commonly used products for CRRT in the management of critically ill patients and a substantial volume of published data exist.

Another extracorporeal endotoxin removal therapy is the hemoperfusion with ToraymyxinTM (PMX) filter, which is a cartridge selectively removing blood endotoxin. PMX is composed of polymyxin B covalently bonded to polystyrene-derivative fibres. It is well known that the polarity of the polymyxin B antibiotic binds endotoxin and has bactericidal activity. Therefore, the rationale underlying extracorporeal therapy with PMX is to remove circulating endotoxin by adsorption.

• Trial with medical device

Inclusion criteria: • Patients with septic shock, defined as 30ml/kg of i.v. fluid administered within a period of 6 hours after initiation of vasopressor therapy with a vasopressor index =3, and at least one of the following criteria: metabolic acidosis, neurologic dysfunction, renal dysfunction, or acute hepatic dysfunction

• Male and Female patients =18 years
• Endotoxin levels =0.6 IU EAA (measured at ICU admission and repeated 24 hours later in case the initial value is =0.4 and <0.6)

Exclusion criteria: • Endotoxin levels <0.6 IU EAA

• Pregnancy or breast feeding
• Neutropenia (circulating neutrophils <500/µl)
• Pre-existing immune deficiencies or immune-suppressive therapy, especially corticosteroids
• Use of Vasopressin (Pitressin?)
• Organ transplantation within the last 12 months
• Terminally ill patients classified as "do not resuscitate"
• History of sensitivity to polymyxin B or to anticoagulant (heparin) HIT or allergy to heparin
• Need for extracorporeal membrane oxygenation (ECMO)