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Flowchart of our Working Procedure. This schematic describes the process instructions for hemoadsorption on ICU and Clinical Study to identify mediators removed by hemoadsorption and documentation of a potential improvement of the patient.
Source publication
Hemoadsorption devices are used to treat septic shock by adsorbing inflammatory cytokines and as yet incompletely defined danger and pathogen associated molecular patterns. In an ideal case, hemoadsorption results in immediate recovery of microvascular endothelial cells’ (mEC) function and rapid recovery from catecholamine-dependency and septic sho...
Citations
... The versatile nature of hemoadsorption may benefit postoperative patients in complex and severely impaired conditions, as CytoSorb ® not only removes cytokines, but also bilirubin, bile acids, myoglobin, some toxins, and various PAMPs and DAMPs [45,[54][55][56]. As with any other blood purification technology, hemoadsorption carries a risk of inadvertent drug removal. ...
Background
Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting.
Methods
A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms “cardiac surgery” and “hemoadsorption”. The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view.
Results
The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability.
Conclusions
The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy.
... Cytokine release also involves the receptor for advanced glycation end products (RAGE) and toll-like receptor (TLR). As a consequence, more leukocytes are attracted to the inflammatory site of tissue damage resulting in systemic inflammation (4,(7)(8)(9)(10). Neutrophils are equipped with various effectors for direct and immediate pathogen defense, such as the release of proteases, particle uptake by phagocytosis and the formation of reactive oxygen species (ROS) such as superoxides and hydrogen peroxides as part of the so-called respiratory burst through NADPH oxidases and superoxide dismutases. ...
... Based on the work of Denzinger et al., the focus was set on the main hypothesis that proteins and DNA -are oxidized by ROS during inflammation. These modified proteins may contribute to a scenario of DAMPs leading to cell injury by targeting different pathways of cell death (7). within 48 hours due to sepsis and had interleukin-6 (IL-6) levels of more than 500 pg/mL and/or renal failure. ...
... An endothelial bioassay and protein chemistry of hemadsorbed materials were applied to identify the most detrimental compounds disrupting endothelial cells. The stepwise approach to first fractionate the hemadsorbed material from a panel of devices from 10 patients, as opposed to a single hemadsorber (7) and test the protein fractions on human endothelial cells rather than rat brain-derived microvascular endothelium as in Denzinger et al. (7), confirmed our previous notion, that a definable composition of molecular entities has the most detrimental effect on endothelial cell layers in vitro. ...
Introduction
In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction.
Material and methods
Plasma materials enriched to hemadsorption filters (CytoSorb®) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry.
Results
Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage.
Conclusion
Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin – cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution.
... Recent in vitro studies suggest that hemoadsorption therapy may improve endothelial function in sepsis by reducing the levels of inflammatory mediators that contribute to endothelial activation and dysfunction [19,20]. Although there is a lot of basic research on the effects of hemoadsorption on endothelial function, there are no clinical studies on whether this approach could actually positively influence the disturbed vascular barrier function under septic conditions. ...
... In a recent experimental study, Jansen et al. [18] confirmed the "proof of principle" for CytoSorb hemoadsorption, showing effective attenuation of circulating cytokine levels during systemic hyperinflammation. Recent investigations in line with previous studies also provide data that the adsorber is capabable of adsorbing endothelial damaging proteins [19,20], suggesting positive effects on endothelial integrity. Knowing the central role of the endothelium in regulating various aspects of homeostasis, and knowing that hyperinflammatory conditions including septic shock lead to endothelial dysfunction resulting in microcirculatory and finally organ failure [9], there seems to be a sound rationale to support endothelial function and integrity by the removal of damaging substances. ...
Recent in vitro studies have investigated the effects of hemoadsorption therapy on endothelial function in sepsis showing a reduction in markers of endothelial dysfunction, but, to this day, there are no clinical studies proving whether this approach could actually positively influence the disturbed vascular barrier function in septic conditions. We retrospectively analyzed data on administered fluid volumes and catecholamines in 124 septic shock patients. We collected catecholamine and volume requirements and calculated the volume balance within different time periods to obtain an assumption on the stability of the vascular barrier. Regarding the entire study cohort, our findings revealed a significant reduction in fluid balance at 72 h (T72) compared to both baseline (T0) and the 24 h mark (T24). Fluid balances from T72–T0 were significantly lower in hospital survivors compared with non-survivors. Patients who received a second catecholamine had a significantly lower in-hospital mortality. Our findings suggest that the applied treatment regimen including hemoadsorption therapy is associated with a reduced positive fluid balance paralleled by reductions in vasopressor needs, suggesting a potential positive effect on endothelial integrity. These results, derived from a large cohort of patients, provide valuable insights on the multiple effects of hemoadsorption treatment in septic shock patients.
... The hemoadsorber is intended as an adjunct therapy that allows for the institution of other interventions that may, in combination, contribute to preventing mortality. Indeed, recent studies have shown effective removal of circulating cytokines [1] and other deleterious materials from the blood [2,3], and have demonstrated an association with lower than predicted rates of mortality in severely ill patients, when combined with other standard-of-care therapies [4,5]. Yet, it is still the primary disease that has to be treated to impact on the patients outcome: as an example, rhabdomyolysis is 'symptomatically' treated by myoglobin removal, but limb ischemia/ crush syndrome tells a different clinical scenario warranting specific therapy. ...
... This study also identified significant amounts of albumin, advanced glycation end products, nucleic acids, oxidized nucleotides, and amyloid-like aggregates in eluted fractions. Obtained fractions were tested in microvascular ECs, where they have resulted in increased apoptotic cell death and reduced ATP production [29]. The current study aimed to identify molecules retained in the CytoSorb adsorbers and to elucidate the effects of the protein extracts eluted from the CytoSorb devices on endothelial cells in vitro. ...
(1) Background: Hemoadsorption is a method of blood purification with a wide spectrum of indications. Pre-emptive use of hemoadsorption in patients undergoing heart surgery with cardiopulmonary bypass is considered to reduce the risk of postoperative systemic inflammatory response syndrome. The current study aimed to identify the spectrum of blood proteins adsorbed on the polymer matrix of the CytoSorb hemoadsorption system and to investigate their influence on cultured endothelial cells in vitro. (2) Methods: Adsorbers used for intraoperative hemoadsorption were obtained from patients undergoing on-pump valve surgery in acute endocarditis. Proteins were extracted from the adsorbers, purified, identified with mass-spectrometry and applied to cultured human aortic endothelial cells. (3) Results: A broad range of blood proteins were identified in the material eluted from the CytoSorb adsorber. When added to cultured ECs, these protein extracts caused severe reduction in cell viability and migration. After 24 h exposure, transcriptional changes with up-regulation of multiple metabolic regulators were observed and verified on the protein level. Genes responsible for control of mitosis were significantly down-regulated. (4) Conclusions: In summary, our data reveal that intraoperative hemoadsorption allows broad spectrum removal of a wide range of molecules eliciting endothelial damage.
... CytoSorb has been shown in multiple studies and case reports to effectively eliminate cytokines and DAMPs (9), reduce vasopressor requirements, limit endothelial damage and play a positive role in survival in adults (10,11). In the observational study of eight pediatric patients Bottari et al. demonstrated that CytoSorb used in conjunction with CRRT was associated with a fast and significant decrease in catecholamine demand, hemodynamic stabilization and an improvement in vasoactiveinotropic score (12). ...
The combination of extracorporeal membrane oxygenation (ECMO) and extracorporeal blood purification in children is rarely used due to small total blood volumes, risks of hemodynamic instability and a negative association between volume of blood transfusion and patient outcome. To our knowledge, this is the first description of a multimodal extracorporeal detoxication in the setting of ECMO in a post-kidney-transplant child on immunosuppression. We describe a case of a 30-months old child, who was extracorporeally resuscitated after cardiac arrest during kidney transplantation surgery and additionally treated with a number of extracorporeal blood purification methods (plasma exchange, CytoSorb, and lipopolysaccharide adsorption) in the setting of immunosuppression therapy. This case report shows the successful use of multimodal extracorporeal therapies for a good patient outcome. The lack of response to CytoSorb therapy might suggest an occult infection and not necessarily failure of treatment.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Recent in-vitro studies have investigated the effects of CytoSorb hemoadsorption on endothelial function in sepsis showing a reduction in markers of endothelial dysfunction, but to this day there is a lack of clinical studies showing whether this approach could actually positively influence the disturbed vascular barrier function in septic conditions. We analyzed the data on administered fluid volumes and catecholamines to determine the potential benefit of CytoSorb hemoadsorption therapy on endothelial function in a clinical scenario. We performed a retrospective analysis of 124 septic shock patients who had undergone adjunctive treatment with CytoSorb hemadsorption therapy. We collected volume requirements, and calculated the volume balance within different time periods to obtain an assumption on the stability of the vascular barrier. We also calculated catecholamine requirements. With regard to the entire study cohort our findings revealed a significant reduction in fluid balance at 72 hours (T72) compared to both baseline (T0) and the 24-hour mark (T24). Fluid balances from T72 – T0 were significantly lower in hospital survivors compared to non-survivors. Patients who received a second catecholamine had a significantly lower in-hospital mortality. Our findings showed that use of hemoadsorption therapy results in a reduced positive fluid balance paralleled by reductions in vasopressor needs suggesting a positive effect on endothelial integrity. These results, derived from a large cohort of patients, provide valuable insights that may greatly improve our understanding of the multiple effects of hemoadsorption treatment in septic shock patients.
Introduction:
Severe cases of the COVID-19 are often associated with the development of a fulminant sepsis-like state with a concomitant cytokine release syndrome. Recently, immunomodulating approaches to treat such a hyperinflammation have come into focus, including the use of new extracorporeal organ support therapies such as CytoSorb hemoadsorption designed to remove cytokines and other circulating mediators from blood.
Patients and methods:
Thirteen critically ill COVID-19 patients with ARDS who received either ECMO therapy and/or CRRT with concomitant multiple organ failure were included. Hemoadsorption therapy was initiated once the patient had established-or was at high risk of developing-a hyperinflammatory state with marked hemodynamic instability or progressive lung failure. Levels of inflammatory markers, vasopressor requirements, oxygenation, and ventilation parameters were measured, as well as clinically relevant outcome measures.
Results:
Combined therapy was associated with a significant reduction in inflammatory mediators, hemodynamic stabilization with a concomitant decrease in requirements for vasoactive substances, and a pronounced improvement in lung function and the need for ventilatory support. Treatment appeared safe and well-tolerated.
Conclusions:
In this case series of SARS-CoV-2 infected patients admitted to the intensive care unit with ARDS, we report effective interleukin (IL)-6 removal, reduced norepinephrine requirement, and improved lung function while receiving adjuvant, extracorporeal hemoadsorption therapy in the context of a multimodal treatment approach. The presented protocol for CytoSorb initiation may be a good foundation for the development of further prospective studies in the field and may eventually also be applied to other forms of hyperinflammatory ARDS.
