Endotoxin adsorption by polymyxin B immobilized fiber column in patients with systemic inflammatory response syndrome: the Japanese experience
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Published on: September 29, 2019
Takashi Sato1, Hisataka Shoji, Nobuhiko Koga
1Kidney Center, Koga Hospital, Kurume, Fukuoka Japan. taka.sato48@h8.dion.ne.jp
Abstract:
The polymyxin B immobilized fiber column (PMX) has been used to treat septic shock patients since 1994 under the Japanese health insurance system. In 1997, the results of the first multicenter clinical study enrolling 42 patients were published, showing a significant reduction in the plasma endotoxin level of the survivors, whilst there was no change with the non-survivors, following treatment with PMX. Body temperature, blood pressure and hemodynamic abnormalities were significantly improved after PMX treatment. The second multicenter study enrolling 88 patients demonstrated that in the survivors, the plasma level of mediators such as TNF-alpha, IL-6, IL-10 and plasminogen activator inhibitor-1 (PAI-1) was significantly decreased following treatment with PMX. Recent studies investigating the mechanisms of PMX treatment have indicated that various mediators other than endotoxin might be adsorbed by PMX. Possible mediators include endogenous cannabinoids, such as macrophage-derived anandamide, and platelet-derived 2-arachidonyl glyceride (2-AG) and tetrahydrobiopterin (BH4), an essential cofactor for inducible NO synthase. The interaction between PMX and activated monocytes may suggest an alternative mechanism for the improvement in patient condition following PMX treatment. Further studies are needed to clarify the mechanisms of PMX treatment and to strengthen the scientific basis of this treatment.
Insights
Polymyxin B (PMX) treatment significantly reduced endotoxin levels and improved patient vitals in septic shock survivors. PMX also decreased inflammatory mediators, suggesting broader therapeutic mechanisms beyond endotoxin removal.
Area of Science:
- Critical Care Medicine
- Nephrology
- Immunology
Background:
- Polymyxin B immobilized fiber (PMX) column therapy has been utilized for septic shock patients in Japan since 1994.
- Initial studies demonstrated PMX effectiveness in reducing plasma endotoxin levels in survivors of septic shock.
Purpose of the Study:
- To evaluate the impact of PMX treatment on plasma endotoxin levels and clinical parameters in septic shock patients.
- To investigate the effect of PMX on inflammatory mediators and explore potential mechanisms of action.
Main Methods:
- Two multicenter clinical studies involving 42 and 88 septic shock patients.
- Analysis of plasma endotoxin levels, body temperature, blood pressure, and hemodynamic parameters pre- and post-PMX treatment.
- Measurement of plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-10, and plasminogen activator inhibitor-1 (PAI-1) in survivors.
Main Results:
- PMX treatment significantly reduced plasma endotoxin levels in survivors but not in non-survivors.
- Significant improvements in body temperature, blood pressure, and hemodynamic status were observed after PMX therapy.
- Survivors showed significantly decreased levels of TNF-α, IL-6, IL-10, and PAI-1 following PMX treatment.
Conclusions:
- PMX therapy is effective in improving clinical outcomes and reducing inflammatory mediators in septic shock patients.
- Mechanisms may involve adsorption of mediators beyond endotoxins, such as cannabinoids and tetrahydrobiopterin (BH4).
- Further research is required to fully elucidate the mechanisms underlying PMX treatment efficacy.
