New cytokine adsorber in use against SIRS and SEPSIS
English translation courtesy of Kardiotechnik Verwaltungsgesellschaft mbH
One of the most common complications during and after cardio-surgery operations using heart-lung machines is the SIRS (Systemic Inflammatory Response Syndrome). Clinically, the spectrum ranges from short-term organ function impairment and failure to multi-organ failure and death. With the CytoSorb adsorber of the American company Cytosorbents cardio-technology has a new treatment option available which safely and effectively removes cytokines and other inflammatory mediators.
Especially high-risk patients or patients with long operation times shall benefit where an excessive immune response (SIRS) or sepsis is expected or already existing. The aim is to regain control over the patient, “Regain Control”, is also the manufacturer’s claim.
The adsorber from the startup from New Jersey which is distributed in Europe by the Cytosorbents Europe GmbH in Berlin consists of highly biocompatible porous high-tech polymer. The “beads” can remove a broad spectrum of inflammatory mediators such as cytokines, chemokines, hormokines and anaphylatoxins. Thus high mediator plasma levels are reduced to a level at which the out-of-control immune response of the body can regain control. In addition, other metabolites such as free hemoglobin, bilirubin or myoglobin with molecule size up to 55 kD can be removed from the blood circulation.
Initial studies and clinical examinations show that besides the high safety of the product (albumin loss <5%, no adsorption of heparin or citrate) that there is a great effectiveness in removing middle molecules, which is clinically beneficial in the treatment of patients with SIRS and sepsis. Thus, e.g. the catecholamine requirement decreases within hours and the patient´s hemodynamic stabilizes faster.
A significant advantage of the new technology is the easy technical use of the adsorbers, which can be used in classic hemoperfusion procedures. The adsorber cartridges can be used with all heart-lung machines (intra-operative use; in the bypass circuit) as well as with existing continuous renal replacement units/CRRT (post-operative use) and can be combined and used parallel with the standard DIN-lock connectors in just a few minutes. Also a use with ECMO equipment is possible which can be done through the combination ECMO-CRRT + CytoSorb. The extracorporeal blood volume of the CytoSorb adsorber is 120ml with blood flow rates between 100-400 ml/min.
In more than 20 studies the efficacy of CytoSorb adsorber is currently being investigated – and the first results are very promising. Crucial for the success of the intra-operative use during long perfusion and ischemia times seem to be two facts: Inflammatory mediators such as IL-6 are effectively reduced, and the effect persists post-operatively, suggesting that the adsorber has influence on the production of interleukins. Animal studies have shown that the activity of NFκB under CytoSorb is reduced.
A first work regarding intra-operative use of CytoSorb for reducing SIRS has recently been presented by a team led by Frank Born, head of the Cardio Technology at the cardiac surgical clinic of the Ludwig Maximilian University in Munich (Kardiotechnik 2/2014, page 41). The Munich team retrospectively compared two groups of 20 patients each with a hypothermic cardiovascular arrest and antegrad brain perfusion. In one group of patients the adsorber was integrated in the extracorporeal circulation (ECC), in the other group it was not.
In the past, there have been several attempts to get at the SIRS by pharmaceutical or medical therapies. But success remained modest or it lacked completely. Thus, for example, it was not possible to achieve enough clinical benefits with the reduction of cytokines and other inflammatory mediators by means of ultra filtration. However, the team led by Born was more successful. There were significant differences in the inflammatory parameters between the two study groups immediately after surgery. The cytokine IL-6 differed significantly throughout the post-operative course between the control and study group, fibrinogen responded with significantly less activation. The leukocytes showed a positive trend in the CytoSorb group and the CRP showed a lower increase in the CytoSorb group and returned to normal more quickly. The procalcitonin was significantly increased in the control group. Born´s conclusion: “By using a cytokine adsorber the physician now has an option available to reduce the overreaction of the immune system.” Further studies will show to what extent these results are transferable to other indications.
Currently there are 40 clinics working with the CytoSorb product in Germany, Austria and Switzerland, internationally there are over 100 hospitals. A first user meeting with more than 50 participants from Germany, Austria and the United States in Leipzig in December gave a thoroughly positive picture of the new technology, which is evoking many hopes among physicians, cardio technicians and scientists, since the treatment of SIRS and sepsis due to the high lethality and mortality urgently needs new adjuvant therapies.