Cytokine and endotoxin removal in critically Ill patients

Endotoxin and cytokine removal by blood purification is one of the most effective treatments for critical illness such as systemic inflammatory response syndrome (SIRS), sepsis and septic shock. SIRS and sepsis frequently associates with hepatic failure, renal failure, respiratory failure, cardiac failure, disseminated intravascular coagulation (DIC) and gastrointestinal bleeding. In these diseases endotoxin and several mediators such as inflammatory cytokines play important roles in clinical course and pathophysiology. The role of blood purification is to remove endotoxin and cytokines, to correct cytokine balance, and to modulate humoral conditions. We use 2 methods of blood purification. One is direct hemoperfusion using Toraymyxin developed by Kodama and Tani in Shiga University of Medical Science. Toraymyxin composed of a Polymyxin B immobilized, can remove endotoxin and can be applied to patients with endotoxemia or suspected bacteremia. The most impressive clinical effectiveness is the improvement of hemodynamic abnormalities. Blood pressure, cardiac index and oxygen consumption index improve after treatment by Toraymyxin. Furthermore inflammatory mediators such as TNF, IL‐6, IL‐10 and plasminogen activator inhibitor‐1 (PAI‐1) are significantly decreased either after 2 h or by the following day in survivors. An immediate mediator, endogenous cannabinoid which is generated by activated monocytes / macrophages and causes septic shock, is also reduced by Toraymyxin treatment. Another method of blood purification is continuous hemofiltration (CHF) and continuous hemodiafiltration (CHDF). CHF and CHDF have been applied only with renal indication, but recently it is widely applied with nonrenal indication for patients with critical illness. The main purpose of CHF and CHDF is to reduce humoral mediators level in blood. As in SIRS patients, inflammatory cytokines are continuously produced in inflammatory regions, the continuous therapy is recommended in ICU. Sometimes inflammatory cytokines are not so reduced in the blood level. The change in the blood level of cytokines depends on the balance between the generation rate and the removal rate of cytokines with continuous therapy. We have some successful results in patients with sepsis and SIRS, but further studies are required to make standardized strategy with blood purification and to have better survival rate.