Shigeto Oda

Abstract:  To evaluate, with a prospective observational study, whether continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter (PMMA‐CHDF) is effective for prevention and treatment of intra‐abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on patients with severe acute pancreatitis (SAP). The study was carried out in the general intensive care unit (ICU) of a university hospital. Seventeen consecutive patients with SAP were treated in the intensive care unit and underwent PMMA‐CHDF whether or not they had renal failure. Blood level of interleukin (IL)‐6, as an indicator of cytokine network activation, and intra‐abdominal pressure (IAP) were measured daily to investigate their time‐course of changes and the correlation between the two. The blood level of IL‐6 was high at 1350 ± 1540 pg/mL on admission to the ICU. However, it significantly decreased to 679 ± 594 pg/mL 24 h after initiation of PMMA‐CHDF (P < 0.05), and thereafter decreased rapidly. Mean intra‐abdominal pressure (IAP) on admission was high, at 14.6 ± 5.3 mm Hg, with an IAP of 20 mm Hg or over in 2 of 17 patients, showing that they had already developed IAH. The IAP was significantly lower (P < 0.05) 24 h after initiation of PMMA‐CHDF, and subsequently decreased. There was a significant positive correlation between blood level of IL‐6 and IAP, suggesting that PMMA‐CHDF improved vascular permeability through elimination of cytokines, and that it thereby decreased interstitial edema to lower IAP. Sixteen of the 17 patients were discharged from the hospital in remission from SAP without development of complications. Continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter appears to be effective for prevention and treatment of IAH in patients with SAP through the removal of causative cytokines of hyperpermeability.

Background/Aims: Cytokines play important roles in the pathophysiology of systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, some effective measures to remove cytokines from the bloodstream could be effective in the treatment of SIRS and sepsis. The aim of this study was to evaluate the cytokine adsorptive property of various adsorbents for the purpose of the development of new selective cytokine adsorption columns. Methods: The cytokine adsorptive property of adsorbent in a CF-X column, which consists of cellulose beads cross-linked with hexamethylene-di-isocyanate, was compared with those of various adsorbents in currently available immunoadsorption columns, such as Immusorba TR®, Immusorba PH®, Selesorb®, and Lixelle®, in vitro batchwise test using patients’ plasma. A newly developed adsorbent, MPCF-X, which was modified by coating the surface of the adsorbent in CF-X with 2-methacryloyloxyethyl phosphorylcholine (MPC), was also tested for its cytokine adsorptive property. Results: The adsorbent in CF-Xshowed a significantly higher adsorption rate for TNF-α, interleukin (IL)-6 and IL-10 compared with other adsorbents (p < 0.05). Adsorbent in Lixelle® showed good affinity to TNF-α and IL-8. Especially, the adsorbent in CF-X almost completely removed TNF-α, whereas it also had considerable affinity to normal IgG. MPCF-X showed decreased affinity to IgG with considerable adsorptive properties to cytokines. Conclusion: Selective cytokine adsorption columns could be developed with improvement of currently available adsorbents. Such a new selective cytokine adsorption column could be clinically applied for the treatment of SIRS/sepsis.

Continuous hemofiltration and continuous hemodiafiltration (CHF/CHDF) were developed as continuous renal replacement therapy for patients with severe conditons and has come to be widely performed mainly in critical care, taking the place of intermittent hemodialysis. The membrane pore size of a hemofilter used for CHF/CHDF allows passage of substances ranging from 30,000 to 50,000 Da, and the method for solute removal in CHF/CHDF employs the principle of convection, which is advantageous for removing middle‐ to high‐molecular‐weight substances. As apheresis therapy to remove pathogenic substances in blood, CHF/CHDF is therefore being investigated for its possible effect on various morbid conditions. It has recently been found that CHF/CHDF removes humoral mediators including cytokines, particularly in severe systemic inflammatory response syndromes such as septic shock and severe acute pancreatitis. CHF/CHDF is thus beginning to be performed for the prevention and treatment of organ dysfunction secondary to septic shock, trauma, or acute pancreatitis. CHF/CHDF is also efficacious as artificial liver support in preventing adverse effects caused by plasma exchange (PE) and for continuous removal of hepatic coma‐inducing substances. CHF/CHDF is effective for various morbid conditions not only as renal replacement therapy, but also as apheresis therapy and is expected to be applied more widely in critical care in the future.

Objective: To evaluate the usefulness of cellular injury score (CIS) and Sepsis-related Organ Failure Assessment (SOFA) score for determination of the severity of multiple organ dysfunction syndrome (MODS). Design: A prospective observational study. Setting: A medical and surgical intensive care unit (ICU) of a teaching hospital. Patients: Forty-seven consecutive MODS patients. Measurements and results: SOFA score and CIS were measured every day for 12 months for 47 MODS patients. Comparison was made of the SOFA score and CIS for usefulness in the scoring of severity of MODS in 26 survivors and 21 non-survivors. In addition, receiver operating characteristics (ROC) analysis was used to determine the usefulness of these two indexes as predictors of prognosis. No significant differences were found on admission between the survivors and non-survivors, but significant differences between the two subgroups (p Conclusions: Both SOFA score and CIS sequentially reflected the severity of MODS. Furthermore, they were comparable in diagnostic value as predictors of prognosis. These findings may indicate the possibility that MODS is a summation of effects of cellular injury. In addition, sequential evaluation of both SOFA score and CIS would provide a more accurate prediction of prognosis than conventional methods.