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 H igh M obility G roup B ox 1 ( HMGB 1). In septic shock, P olymyxin‐ 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 HMGB 1 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‐ HMGB 1 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 S equential O rgan F ailure A ssessment ( 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.