During sepsis toxins released from, e.g., bacteria induce reactions of various cascade systems that may cause progression of the patient into septic shock, disseminated intravascular coagulation, multiorgan dysfunction syndrome and subsequent death. The use of conventional treatments using antibiotics, fluid substitution, inotropic drugs, respiration aid and dialysis is not enough to reverse the serious prognosis. The addition of various other drugs such as antibodies against various cytokines and cytokine receptors, pentoxiphylline, immunoglobulins or high doses of steroids is usually without benefit for the prognosis of the patient. Another possibility to reduce the extent of toxins and other harmful compounds in the circulation is the use of apheresis (removal by technical devices). This can be done either in a nonselective way (plasma exchange, plasmapheresis) or more selectively using various adsorbers such as polymyxin B. The survival in studies varies between 50 and 80%. Besides the use of nonselective apheresis, the development of various selective adsorption techniques may be one approach to improve survival of these severely ill patients.

Is there a future for adsorption techniques in sepsis

Dieter Falkenhagen was born in 1942 in Dresden, Germany and died in 2015. He specialized in internal medicine and nephrology. Focusing on artificial organ research, he investigated various aspects of the efficacy and safety of hemodialysis and adsorption technologies, including biocompatibility issues related to blood versus surface interactions and the adverse effects of endotoxin contamination. He studied various mathematical models to analyze efficacy and safety, and animal models to help clarify uncertainty issues. Through his studies, adsorbents were developed, resulting in Prometheus, an artificial liver support device. Anticoagulation models, including citrate perfusion, were improved and made safer by his work. He also stepped into bioreactor research to increase efficacy of liver support devices.

Dieter Falkenhagen (1942-2015): a multifaceted scientist

A method to treat cancer uses ultrapheresis, refined to remove compounds of less than 120,000 daltons molecular weight, followed by administration of replacement fluid, to stimulate the patient's immune system to attack solid tumors. In the preferred embodiment, the patient is ultrapheresed using a capillary tube ultrafilter having a pore size of 0.02 to 0.05 microns, with a molecular weight cutoff of 120,000 daltons, sufficient to filter one blood volume. The preferred replacement fluid is ultrapheresed normal plasma. The patient is preferably treated daily for three weeks, diagnostic tests conducted to verify that there has been shrinkage of the tumors, then the treatment regime is repeated. The treatment is preferably combined with an alternative therapy, for example, treatment with an anti-angiogenic compound, one or more cytokines such as TNF, gamma interferon, or IL-2, or a procoagulant compound. The treatment increases endogenous, local levels of cytokines, such as TNF. This provides a basis for an improved effect when combined with any treatment that enhances cytokine activity against the tumors, for example, treatments using alkylating agents, doxyrubicin, carboplatinum, cisplatinum, and taxol. Alternatively, the ultrapheresis treatment can be combined with local chemotherapy, systemic chemotherapy, and/or radiation.

Method and system to remove cytokine inhibitor in patients

Method and compositions for treatment of cancers

Severe sepsis and multiorgan dysfunction syndrome may develop in the course of severe sepsis, intoxication, poisoning, crush injury, asystole, drowning, and several other complications. When normal intensive care is insufficient despite vasoactive drugs, respiratory aid, and dialysis, the risk for death is extremely high. Only very little benefit has been noted in various trials using drug administration such as antibodies against TNF-alfa, immunoglobulin, pentoxifylline and high dose steroids. The use of apheresis (plasma exchange, plasmapheresis, adsorption) to remove toxins, cytokines, and other compounds has been tried in an unselective as well as selective manner. Data now exists that indicate increased survival by this type of therapy. It is time to focus on randomised controlled trials with these techniques to decide the efficacy of apheresis in this area.

Is There a Place for Apheresis in Patients with Severe Sepsis or Multi Organ Dysfunction Syndrome

Multiorgan failure (MOF) based on septic processes is very common but prognostically an extremely severe disease that has to be treated exclusively under intensive care conditions. Extracorporeal blood purification (ECBP) using specific and efficient systems such as the microspheres based detoxification system (MDS) (Artif Organs 1996;20:420) could improve significantly the situation of MOF in terms of the efficient removal of endotoxins as well as key mediators such as tumor necrosis factor alpha (TNF alpha). The purpose of the study was to test the effectiveness of endotoxin and cytokine removal to blunt cellular response. In terms of the in vitro principle methodology, isolated peripheral blood mononuclear cells (PBMC) were incubated with endotoxins and a selective endotoxin adsorbent, which was added at various times (immediately or 30, 60, 120, 240, or 360 min) after the onset of incubation. TNF alpha release of monocytes was measured following a standard procedure after 20 h. Human TNF alpha was incubated with cultured human endothelial cells with and without a specific TNF alpha adsorbent (polyclonal antibodies coated on polystyrene particles). The results showed that after the initial addition of endotoxins, the activation of monocytes can be stopped within 120 min by addition of endotoxin adsorbents. In addition, specific TNF alpha adsorbents are able to prevent intercellular adhesion molecule 1 (ICAM-1) expression of endothelial cells, therefore avoiding activation of endothelial cells. In conclusion, cell culture models are suitable to simulate cell interaction in MOF. Specific adsorbents are able to reduce or block pathophysiologically relevant cell interactions, and the time frame for effective ECBP seems to be very short, and therefore, efficiency must be high.

In Vitro Cell Culture Systems as the Basis for an Extracorporeal Blood Purification Strategy In Multiorgan Failure Treatment

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In Vitro Cell Culture Systems as the Basis for an Extracorporeal Blood Purification Strategy In Multiorgan Failure Treatment