CytoSorb-XL is a new polymer bead technology under advanced development that combines lipopolysaccharide (LPS) endotoxin removal with the cytokine, toxin, and inflammatory mediator reduction achieved by CytoSorb®. CytoSorb-XL is expected to eliminate the need for stand-alone endotoxin specific filters by offering superior performance in the removal of not just endotoxin, but a much broader array of inflammatory mediators that drive uncontrolled deadly inflammation, organ failure, and death in sepsis.
Endotoxin, produced by Gram negative bacteria such as E. coli, is a potent and deadly trigger of severe sepsis and septic shock. It does so through binding to the toll-like receptor-4 (TLR4) on white blood cells that activates the immune system and generates a massive, maladaptive systemic inflammatory response syndrome (SIRS) through cytokine storm. Interestingly, normally lethal doses of endotoxin in mice that lack the TLR4 receptor and cannot recognize endotoxin, do not activate the immune response and are not harmful.1 These findings demonstrate that it is the excessive activation of the immune response, and not endotoxin directly, that causes the toxicity. That said, in patients that can recognize endotoxin, endotoxin likely synergizes with cytokines and other inflammatory mediators to prolong an uncontrolled SIRS response. This helps to explain why endotoxin removal alone has not been shown to be effective in the treatment of severe sepsis or septic shock, and why the simultaneous removal of endotoxin, cytokines, exotoxins, and other inflammatory mediators is anticipated to be much more efficacious. Because of this, CytoSorb-XL has the potential to be a superior treatment of sepsis and septic shock compared to other standalone therapies.
Sepsis is the overzealous immune response to a life-threatening infection often leading to organ dysfunction, organ failure, and death. According to the Global Sepsis Alliance, sepsis afflicts an estimated 30 million people each year, is more common than a heart attack, and claims more lives than any cancer, killing one person every 3-4 seconds. Sepsis remains the primary cause of death following an infection and remains a top 10 killer worldwide. The Agency for Healthcare Research and Quality (AHRQ) lists sepsis as the most expensive condition treated in U.S. hospitals, costing $23.7 billion in 2013, accounting for 6.2% of the aggregate cost of all hospitalizations.
1 Hoshino K, et al “Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product” J Immunol 1999 Apr 1; 162(7):3749-52.