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When septic multiple organ dysfunction syndrome (MODS) occurs as a result of endotoxemia, diverse chemical mediators are excessively produced, and the patient becomes seriously ill. Under such circumstances, it is difficult to improve the patient's condition by endotoxin apheresis alone and hemodiafiltration should be carried out to remove excessive chemical mediators. Series-parallel treatment combining continuous endotoxin apheresis and hemodiafiltration is recommended for patients with septic MODS.

Nine patients with postoperative liver failure were treated with plasma exchange (PE) or PE and continuous hemodiafiltration (CHDF), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the PE group and the PE + CHDF group (P < 0.0001 and P < 0.0001, respectively), the percentage of the increase in citrate levels was significantly higher in the PE group than in the PE + CHDF group (P = 0.0051). Total bilirubin (T-Bil) levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0.0001 and P = 0.0001, respectively). There were no significant differences in T-Bil levels between the two groups (P = 0.5181). There were no significant differences in interleukin (IL)-6 levels before and after treatment in both the PE and PE + CHDF groups (P = 0.1281 and P = 0.2273, respectively). IL-18 levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0.0001 and P = 0.0002, respectively), but there were no significant differences in the removal rate of IL-18 in both the PE and PE + CHDF groups (P = 0.8749). These results indicate that combining PE and CHDF in a series-parallel circuit is an effective modality for suppressing the elevation of blood citrate levels. This finding may have important implications for the development of an effective treatment for patients with postoperative liver failure.

We developed a series-parallel treatment method for combined plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy in fulminant hepatitis. We then compared total serum bilirubin, citrate, and cytokine levels obtained by the new methods to those obtained with treatment by the single and reverse-parallel PE methods. Ten adult patients with fulminant hepatitis consented to participate. Plasma exchange was conducted 25 times by the single method (PE only), 16 times by the reverse-parallel method, and 37 times by the series-parallel method. The percentage of total bilirubin removed was highest with the single method followed in order by that with the series-parallel and reverse-parallel methods; the differences were significant. The percentage increase in citrate level was highest with the single method, followed in order by that with the series-parallel and the reverse-parallel methods; these differences were also significant. There was no significant difference in serum interleukin (IL)-6 levels after PE, by the single or the reverse-parallel methods. However, the IL-6 level decreased significantly following PE by the series-parallel method. The serum IL-18 level decreased significantly following PE by each of the three methods. Thus, removal of excess bilirubin, citrate, and cytokines by the series-parallel method, a simple maneuver with excellent removal rates, was considered effective.

Plasma exchange has gained widespread acceptance as an effective mode of blood purification in patients suffering from acute hepatic failure. However, it is still undetermined whether a single use of plasma exchange is capable of removing inflammatory cytokines completely or of preventing the development of citrate toxicity inherent with fresh frozen plasma. To clarify these issues we developed combined plasma exchange and continuous hemodiafiltration (CHDF) modality in which CHDF is performed in an opposite direction to plasma exchange. This study was designed to assess the effectiveness of combined modality therapy. Fifteen patients with acute hepatic failure were treated with plasma exchange (plasma exchange group) or plasma exchange and CHDF (plasma exchange + CHDF group), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the plasma exchange group and the plasma exchange + CHDF group, the percentage of the increase in citrate levels was significantly higher in the plasma exchange group than in the plasma exchange + CHDF group. Bilirubin levels were significantly lower after treatment in both the plasma exchange and plasma exchange + CHDF groups. There were no significant differences in tumor necrosis factor-alpha levels before and after treatment in the plasma exchange group, but they were significantly lower after treatment in the plasma exchange + CHDF group. Interleukin-6 (IL-6) levels increased significantly after treatment in the plasma exchange group, but there were no significant differences in the IL-6 levels before and after treatment in the plasma exchange + CHDF group. Interleukin-8 levels increased significantly after treatment in the plasma exchange group while decreasing significantly after treatment in the plasma exchange + CHDF group. These results indicate that combining plasma exchange and CHDF in a parallel circuit is an effective modality for suppressing the elevation of blood citrate levels and for removing inflammatory cytokines. This finding may have important implications for the development of an effective treatment for patients with acute hepatic failure.