Effective combination therapy of polymyxin-B direct hemoperfusion and recombinant thrombomodulin for septic shock accompanied by disseminated intravascular coagulation: a historical controlled trial.

Abstract

Disseminated intravascular coagulation (DIC) and multiple organ failure often occur via the crosstalk between inflammation and coagulation, which is mediated by High Mobility Group Box 1 (HMGB1). In septic shock, Polymyxin-B direct hemoperfusion (PMX-DHP) ameliorates hemodynamics by endogenous cannabinoid adsorption and improves pulmonary oxygenation by indirect cytokine reduction through the adsorption of activated mononuclear cells. However, PMX-DHP has no direct effect on HMGB1 circulating in the plasma. In cases with DIC, recombinant thrombomodulin (rTM), an effective drug for DIC, exerts not only anticoagulation but also antiinflammatory properties via direct anti-HMGB1 activity. Therefore, a combination of PMX-DHP and rTM is expected to block the vicious cycle of a cytokine storm ending up with multiple organ failure in DIC. The aim of this study was to investigate the efficacy of combination therapy for septic shock associated with DIC. This study comprised 22 consecutive patients with sepsis-induced DIC who received PMX-DHP. The initial eight patients were treated without rTM (historical control group), and the following 14 patients were given rTM (rTM group). The baseline Sequential Organ Failure Assessment (SOFA) score or age was not different between both groups. Sixty-day survival rate in the rTM group was significantly higher than that in the control group (85.7% vs. 37.5%, P = 0.015). A combination of PMX-DHP and rTM may be effective in septic shock accompanied by DIC and is expected to improve survival rates.

• Authors: Masafumi Yamato, Yusuke Minematsu, Junya Fujii, Kohei Mori, Takumi Minato, Sachie Miyagawa, Ryuta Fujimura, Naoko Morikage, Yuka Arata, Chisako Nakano, Akira Wada, Takahito Ito
• Journal: Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy (Ther Apher Dial) Vol. 17 Issue 5 Pg. 472-6 (Oct 2013) ISSN: 1744-9987 [Electronic] Australia
• PMID: 24107274 (Publication Type: Journal Article)
• Copyright: © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

Chemical References

• Cytokines
• Endocannabinoids
• HMGB1 Protein
• Recombinant Proteins
• Thrombomodulin
• Polymyxin B

Topics

• Aged
• Cytokines (metabolism)
• Disseminated Intravascular Coagulation (etiology, therapy)
• Endocannabinoids (metabolism)
• Female
• Follow-Up Studies
• HMGB1 Protein
• Hemoperfusion (methods)
• Humans
• Male
• Multiple Organ Failure (etiology, therapy)
• Polymyxin B (administration & dosage)
• Recombinant Proteins (therapeutic use)
• Retrospective Studies
• Shock, Septic (complications, therapy)
• Survival Rate
• Thrombomodulin (administration & dosage, therapeutic use)