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Sepsis frequently leads to multiple organ failure due to the uncontrolled amplification and spread of inflammation, even if the infectious source is controlled. Lipopolysaccharide (LPS), a typical pathogen-associated molecular pattern (PAMP), is adsorbed by the polymyxin B-immobilized fiber column (PMX). PMX has been used for decades in Europe. Results of a North American randomized controlled trial (RCT) on PMX have recently been announced in a press release; results of large-scale observational studies and meta-analyses have also been reported in the last several years.To date, 3 multicenter RCTs on PMX hemoperfusion have been conducted outside of Japan. All of them enrolled postoperative patients with sepsis or septic shock secondary to intra-abdominal infection. However, confidence in the level of evidence provided by these RCTs is very low. Results from recent propensity-matched analyses and meta-analyses indicate that PMX hemoperfusion may improve survival outcomes among patients with sepsis. LPS is an important causative PAMP in sepsis; it triggers the immune response. PMX adsorbs LPS by using a polymyxin B-immobilized fiber that has high affinity for LPS. Moreover, PMX has other mechanisms of action, such as endogenous cannabinoid and activated neutrophil and monocyte adsorption, monocyte surface antigen alteration, and regulation of apoptosis in renal tubular cells. Furthermore, clinical research shows that PMX hemoperfusion can improve patients' hemodynamic status and pulmonary oxygenation and can sustain its endotoxin adsorption capability beyond 2 h. Improved pulmonary oxygenation among patients with sepsis-associated acute respiratory distress syndrome is linked to the effectiveness of PMX hemoperfusion in treating acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). Key Messages: Meta-analysis indicates that PMX hemoperfusion may improve the survival outcomes of patients with sepsis; LPS adsorption is an important treatment modality in sepsis. Many novel findings on the mechanisms of action of PMX, beyond endotoxin adsorption, have been reported. Additionally, a prolonged duration of PMX hemoperfusion has been shown to be efficacious, and beneficial effects on AE-IPF have been demonstrated. The use of PMX hemoperfusion for the correct duration and at the right time in appropriate patients may lead to favorable therapeutic outcomes.

In response to a request from the French government, Rhône-Poulenc started development of a synthetic membrane for dialysis in 1969. When used for patients the new membrane, AN69, showed improved efficiency and clinical outcome. Treatment times could be reduced, peripheral neuropathy improved and patients expressed improved quality of life. This was the introduction of high-flux, volume-controlled dialysis. The polymer used for the AN69 membrane is a copolymer of acrylonitrile and sodium methallylsulfonate, specially selected for the dialysis application. Contrary to most synthetic membranes AN69 is hydrophilic, because the numerous sulfonate groups attract water and create a hydrogel structure which provides high diffusive and hydraulic permeability. In the AN69 membrane the microstructure and the chemical composition offer a unique context for bulk adsorption of low-molecular-weight proteins, the high water content of the hydrogel making the polymer chains easily accessible. The highly specific adsorptive properties - limited on the surface and favored in the membrane structure and with high specificity for basic, medium-sized proteins - distinguish AN69 from other synthetic high-flux membranes as well as from other so-called adsorptive membranes in the field of dialysis. Since its creation in the early 1970s the AN69 membrane has evolved to meet the requirements and challenges of dialysis therapy. Still the basic characteristics of high permeability to fluid and to a wide range of relevant uremic retention products combined with excellent biocompatibility, whether measured by traditional or novel indicators, have remained the hallmark of the membrane. The unique adsorptive capacity has provided a base for further development. The latest version of AN69, HeprAN, has heparin grafting on the inner surface and enhanced adsorption of bacterial products on the outer surface. Modern versions of AN69 are today used in hemodialysis and contemporary modes of convective therapies for a large number of chronic as well as acute renal patients around the world.

Sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) is an effective, intensive modality for sepsis treatment. Here we describe the effectiveness of SHEDD-fA, which makes the best use of three principles: dialysis, filtration and adsorption, for mediator removal in the treatment of severe sepsis. SHEDD-fA was initiated after adequate fluid resuscitation and catecholamine support had been provided. A large (2.1 m(2)) polymethylmethacrylate membrane dialyzer was placed in the blood circuit. Operation conditions were as follows: blood flow rate 150 ml/min, filtration rate 1,500 ml/h (post-dilution), and dialysate flow rate 300-500 ml/min over 8-12 h daily. 55 consecutive patients with severe sepsis were studied. The following results were obtained: pressure catecholamine index significantly decreased at 3 h after initiation of septic shock, PaO(2)/F(IO2) significantly increased at 1 h after initiation of septic acute respiratory distress syndrome, a significant decrease in interleukin (IL)-6 level for 3 days was observed, and IL-6 was effectively adsorbed in one pass through the filter. The average sequential organ failure assessment score of patients was 10.1 and the mortality at 28 days was 16.4% (46 survived, 9 died). Because SHEDD-fA is an intensive and high-efficiency modality, removal of useful drugs or nutrients may be observed. Despite the fact that removal of useful substances cannot be ignored, we believe that an appropriate stage or timing can be identified so that we can avoid a vicious cycle and use blood purification with effective diffusion, filtration and adsorption. We demonstrate that SHEDD-fA may be an effective, intensive modality for the treatment of patients with severe sepsis and is a possible modality for cytokine modulation therapy.