Kellum John A, Kamaluddin Esha, Foster Debra
Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Spectral Medical Inc, Toronto, Ontario, Canada.
Blood Purif. 2025 Mar 11:1-12. doi: 10.1159/000544989.
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 cases, 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.
In septic patients, evidence for the use of hemofiltration and therapeutic plasma exchange, 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, allow 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 20R, Toxipak sorption column) and those for which endotoxin removal is included in a more broad-spectrum device (Efferon LPS, oXiris).
While only a small number of devices are currently available in the TREA class of EBP, there is an opportunity here to bring precision medicine to sepsis.
从历史上看，脓毒症的体外血液净化（EBP）治疗主要用作多器官功能衰竭管理的辅助治疗，而不是针对清除导致疾病状态的体内毒素。大约10% - 15%的脓毒症病例，或约三分之一至一半的感染性休克患者，血液中内毒素活性水平较高。人类对内毒素极其敏感，这使得内毒素性感染性休克（ESS）特别致命。如今，我们有一种新兴的针对内毒素的EBP类别——靶向快速内毒素吸附（TREA），可用于ESS的治疗。
在脓毒症患者中，很难获得使用血液滤过和治疗性血浆置换这两种最常见的EBP形式的证据。此外，针对多种溶质进行清除的广谱EBP疗法一直在努力确定合适的患者。脓毒症患者的先天免疫反应存在显著的临床异质性。相比之下，靶向EBP疗法涉及测量单一溶质，然后选择合适的疗法来针对其清除，从而能够具体选择合适的患者。不幸的是，测量目标可能具有挑战性。可以使用内毒素活性测定法在全血中测量内毒素。然而，由于完整内毒素分子的大小，它不能通过血液滤过膜过滤。吸附仅需要血液或血浆与吸附剂接触，因此是针对其清除的合适模式。TREA技术包括专门针对内毒素的设备（Alteco LPS吸附器、MATISSE吸附器、Toraymyxin 20R、Toxipak吸附柱）以及内毒素清除包含在更广谱设备中的那些（Efferon LPS、oXiris）。
虽然目前TREA类EBP中仅有少数设备可用，但这里有机会将精准医学应用于脓毒症。
