Extracorporeal Removal of Endotoxin

Bacterial sepsis is a major cause of fatality worldwide and the increasing multidrug-resistant bacteria is a major concern for public health and modern health systems (Breijyeh et al., Molecules 25(6):1340, 2020). Sepsis is a multi-step process that involves an uncontrolled inflammatory response by the host cells that may result in multi organ failure and death. Both gram-negative and gram-positive bacteria play a major role in causing sepsis. Surviving Sepsis Campaign recommends urgent stabilization of the patient, volume resuscitation, vasopressors and/or inotropic therapy to restore perfusion, and the administration of broad spectrum, empirical antibiotic therapy in the setting of an intensive care unit (ICU) (Evans et al., Intensive Care Med 47(11):1181-1247, 2021). However, antibiotic-induced release of bacterial cell wall components can have immediate adverse effects for the patient (Schulze et al., Res Exp Med 200: 169-174, 2001; Lepper et al. Intensive Care Med 28: 824-833, 2002). Particularly, some classes of beta-lactam antibiotics lead to markedly increased levels of free endotoxins while treatment with carbapenems and aminoglycosides produces relatively low amounts of endotoxins. Polymyxins are effective (Trimble et al., Cold Spring Harb Perspect Med 6(10):a025288, 2016; Lepper et al., Intensive Care Med 28(7):824-33, 2002) and able to bind to endotoxin (LPS) and phospholipids in the outer cell membrane of Gram-negative bacteria. However, systemic administration of polymyxin B (PMX-B) in humans is restricted because of its nephrotoxicity and neurotoxicity. Nowadays, new techniques based on the extracorporeal circulation of blood have been developed. In this chapter, we will review the effect of extracorporeal removal of endotoxin. Particularly, PMX-B is a strong ligand for the extracorporeal selective adsorption of circulating endotoxin in blood (Tani et al., Adv Exp Med Biol 1145:321-341, 2019), largely described in literature, and for this reason it will be depicted in detail in the present chapter.