Extracorporeal Endotoxin Removal
by Direct Hemoperfusion with PMX
Among the various strategies studied to eliminate endotoxin, Polymyxin-B hemoperfusion has been the most effective in blocking the toxic effects of endotoxin by virtue of its electrochemical affinity with Lipid A (common to all species of endotoxin). However, systemic use of Polymyxin-B is limited by severe nephro- and neurotoxicity.
The interaction between Polymyxin-B and Lipid A of endotoxin is governed primarily by forces which include:
Ionic: guides the formation of the link/bond;
Hydrophobic: breaks the spatial order of the acyl chains of LPS and neutralizes the toxicity, transforming LPS and Polymyxin-B into a single unimolecular compound.
PMX (Toraymyxin hemoperfusion) removes endotoxin from the blood using the electrochemical properties of Polymyxin-B, while avoiding known side effects of its systemic administration. The PMX cartridge contains polystyrene composite woven fibre with Polymyxin-B immobilized on the surface through covalent bonding. The blood flows radially and uniformly through the fibres at a rate of 80-120 ml/min before exiting the cartridge. The recommended dosing of hemoperfusion is two 2-hour hemoperfusion events in a 24 hour period. The in-vitro adsorption capacity (human blood) was measured as 20 μg (Romaschin et al., 2017).
PMX selectively adsorbs circulating endotoxin, thereby helping to rebalance the innate immune system. Removal of endotoxin leads to a decrease in inflammatory mediator levels (shown in the figure below), as well as an improvement in vascular function and hemodynamics.
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