Targeted Rapid Endotoxin Adsorption (TREA): can we bring precision medicine to sepsis?

Background: Historically, extracorporeal blood purification (EBP) treatment for sepsis was mainly used as an adjunctive therapy for the management of multiple organ failure rather than targeting the removal of toxins from the body that are contributing to the disease state. Approximately 10-15% of sepsis, or approximately one third to half of patients with septic shock, exhibit high levels of endotoxin activity in their blood. Humans are exquisitely sensitive to endotoxin making endotoxic septic shock (ESS) particularly deadly. Today, we have an emerging class of EBP that is specific to endotoxin – Targeted Rapid Endotoxin Adsorption (TREA) – that can be used for the treatment of ESS. Summary: In septic patients, evidence for the use of hemofiltration and therapeutic plasma exchange (TPE), the two most prevalent forms of EBP, has been difficult to obtain. Additionally, broad-spectrum EBP therapies that target multiple solutes for removal have struggled to identify the right patients. There is significant clinical heterogeneity of the innate immune response across patients with sepsis. In contrast, targeted EBP therapies which involve measuring a single solute then choosing appropriate therapy to target its removal, allows for the specific selection of a suitable patient. Unfortunately, measuring the target can prove challenging. Endotoxin can be measured in whole blood using the endotoxin activity assay. However, owing to the size of intact endotoxin molecule, it cannot be filtered using hemofiltration membranes. Adsorption, which only requires the contact of blood or plasma with a sorbent is therefore a suitable model to target its removal. TREA technologies include devices that specifically target endotoxin (Alteco LPS Adsorber, MATISSE Adsorber, Toraymyxin 20-R, Toxipak sorption column) and those for which endotoxin removal is included in a more broad-spectrum device (Efferon LPS, oXiris).