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Background The CytoSorb hemoadsorption device has been demonstrated to be capable of clearing inflammatory cytokines, but has not yet been shown to attenuate plasma cytokine concentrations. We investigated the effects of CytoSorb hemoperfusion on plasma levels of various cytokines using the repeated human experimental endotoxemia model, a highly standardized and reproducible human in vivo model of systemic inflammation and immunological tolerance induced by administration of bacterial lipopolysaccharide (LPS). Methods Twenty-four healthy male volunteers (age 18–35) were intravenously challenged with LPS (a bolus of 1 ng/kg followed by continuous infusion of 0.5 ng/kg/hr for three hours) twice: on day 0 to quantify the initial cytokine response and on day 7 to quantify the degree of endotoxin tolerance. Subjects either received CytoSorb hemoperfusion during the first LPS challenge (CytoSorb group), or no intervention (control group). Plasma cytokine concentrations and clearance rates were determined serially. This study was registered at ClinicalTrials.gov (NCT04643639, date of registration November 24th 2020). Results LPS administration led to a profound increase in plasma cytokine concentrations during both LPS challenge days. Compared to the control group, significantly lower plasma levels of tumor necrosis factor (TNF, − 58%, p  < 0.0001), interleukin (IL)-6 ( − 71%, p  = 0.003), IL-8 ( − 48%, p  = 0.02) and IL-10 ( − 26%, p  = 0.03) were observed in the CytoSorb group during the first LPS challenge. No differences in cytokine responses were observed during the second LPS challenge. Conclusions CytoSorb hemoperfusion effectively attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo, whereas it does not affect long-term immune function. Therefore, CytoSorb therapy may be of benefit in conditions characterized by excessive cytokine release.

Background Septic shock, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a highly lethal condition that causes substantial morbidity and mortality among critically ill patients. One of the hallmarks of sepsis is the excessive release of cytokines and other inflammatory mediators causing refractory hypotension, tissue damage, metabolic acidosis and ultimately multiple organ failure. In this context, cytokine reduction by hemoadsorption represents a new concept for blood purification, developed to attenuate the overwhelming systemic levels of pro-inflammatory and anti-inflammatory mediators released in the early phase of sepsis. Methods In the present case series, we evaluated the impact of a new hemoadsorption device (CytoSorb) used as adjunctive therapy, on hemodynamics and clinically relevant outcome parameters in 26 critically ill patients with septic shock and in need of renal replacement therapy. Results We found that treatment of these patients with septic shock was associated with hemodynamic stabilization and a reduction in blood lactate levels. Actual mortality in the overall patient population was lower than mortality predicted by acute physiology and chronic health evaluation II (APACHE II). These effects seem to be more pronounced in patients in whom therapy started within 24 h of sepsis diagnosis, whereas a delay in the start of therapy was associated with a poor response to therapy in terms of reduction of catecholamine demand and survival. Moreover, from our patient population, medical patients seemed to benefit more than post-surgical patients in terms of survival. Treatment using the CytoSorb device was safe and well-tolerated with no device-related adverse events during or after the treatment sessions. Conclusion Hemoadsorption using CytoSorb resulted in rapid hemodynamic stabilization and increased survival, particularly in patients in whom therapy was started early. Given the positive clinical experience of this case series, randomized controlled trials are urgently needed to define the potential benefits of this new treatment option.

To evaluate hemoadsorptive therapy in treating refractory septic shock in a non-concurrent cohort of patients by analyzing clinical and laboratory parameters. A non-concurrent review of patients admitted to the intensive care unit (ICU) with refractory septic shock who received hemoadsorptive therapy over five years was conducted. Clinical variables, including age, gender, APACHE II and SOFA scores, vasopressor requirements, and laboratory parameters, as well as in-hospital mortality and mortality at 30 and 90 days, were analyzed. Descriptive statistics were calculated, and pre- and post-therapy variables were compared using the Mann-Whitney test. The median age of the cohort was 65.5 years, with a male-to-female ratio of 0.43. Hemoadsorptive therapy was associated with a reduction in vasopressor requirements, with a median initial noradrenaline requirement of 0.7 μg/kg/min (IQR 0.45–0.8875) decreasing to 0.12 μg/kg/min (IQR 0–0.225) post-therapy. The total normalized vasopressor requirement at the beginning of the therapy was 0.8125 (IQR 0.56–1.08), and post-therapy, it was 0.175 (IQR 0.01–0.29). Adrenaline was used in 0.64 of patients, vasopressin in 0.43, and 0.28 received inotropic therapy. Median APACHE II scores pre- and post-therapy were 30.5 and 20.5, respectively, while SOFA scores were 13.5 and 11.5. Both scores decreased without statistical significance according to the Wilcoxon test. Median lactate levels decreased by 62%, from 7,86 mmol/l pre-therapy to 2,97 mmol/l post-therapy. Inflammatory parameters, such as C-reactive protein (CRP), decreased from 206 mg/dL to 180 mg/dL, and procalcitonin (PCT) decreased from 58 to 8.91. In-hospital mortality was 0.57, increasing to an index of 0.64 at 90 days of follow-up. Eight out of 14 patients died during hospitalization, with an additional patient succumbing to the illness within the 90-day follow-up period. Hemoadsorptive therapy demonstrated encouraging efficacy in the management of refractory septic shock in our non-concurrent cohort of 14 patients. A significant decrease in vasopressor requirements, lactate levels, and inflammatory parameters was observed, although changes in APACHE II and SOFA scores were not statistically significant. These promising results warrant further investigation through larger cohort studies to evaluate the impact of hemoadsorptive therapy on long-term mortality and to explore its potential role as a standard treatment option for refractory septic shock.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris®-AN69 membrane, CytoSorb® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.

The aim of this proof of concept, prospective, randomized pilot trial was to investigate the effects of extracorporeal cytokine removal (CytoSorb®) applied as a standalone treatment in patients with septic shock. 20 patients with early (<24 h) onset of septic shock of medical origin, on mechanical ventilation, norepinephrine>10 μg/min, procalcitonin (PCT) > 3 ng/mL without the need for renal replacement therapy were randomized into CytoSorb (n = 10) and Control groups (n = 10). CytoSorb therapy lasted for 24 h. Clinical and laboratory data were recorded at baseline (T0), T12, T24, and T48 hours. Overall SOFA scores did not differ between the groups. In the CytoSorb-group norepinephrine requirements and PCT concentration decreased significantly (norepinephrine: CytoSorb: T0 = 0.54[IQR:0.20–1.22], T48 = 0.16[IQR:0.07–0.48], p = .016; Controls: T0 = 0.43[IQR:0.19–0.64], T48 = 0.25[IQR:0.08–0.65] μg/kg/min; PCT: CytoSorb: T0 median = 20.6[IQR: 6.5–144.5], T48 = 5.6[1.9–54.4], p = .004; Control: T0 = 13.2[7.6–47.8], T48 = 9.2[3.8–44.2]ng/mL). Big-endothelin-1 concentrations were also significantly lower in the CytoSorb group (CytoSorb: T0 = 1.3 ± 0.6, *T24 = 1.0 ± 0.4, T48 = 1.4 ± 0.8, *p = .003; Control: T0 = 1.1 ± 0.7, T24 = 1.1 ± 0.6, T48 = 1.2 ± 0.6 pmol/L, p = .115). There were no CytoSorb therapy-related adverse events. This is the first trial to investigate the effects of early extracorporeal cytokine adsorption treatment in septic shock applied without renal replacement therapy. It was found to be safe with significant effects on norepinephrine requirements, PCT and Big-endothelin-1 concentrations compared to controls. Trial registration: The study has been registered on ClinicalTrials.gov, under the registration number of NCT02288975, registered 13 November 2014. •First randomized trial on one single 24-hour period of standalone CytoSorb treatment•Medical patients with septic shock were randomized (CytoSorb treated or control)•Patients were treated for 24 h with CytoSorb in addition to standard treatment•Significant reduction (70%) in norepinephrine requirement, PCT and Big Endothelin-1

Hemoadsorption with CytoSorb® offers a possible therapeutic approach in septic shock, but modes of application and dosing are still undetermined. Data from surgical patients with septic shock, treated with hemoadsorption adjunctive to renal replacement therapy were analyzed retrospectively. The 28-day mortality was compared to predicted mortality. In 70 patients (70.6 ± 13.3 years), hemoadsorption was applied for 85.6 ± 53.8 h. The APACHE ll (30.2 ± 6.3) calculated to a predicted mortality of 73.3%, while the observed mortality was significantly lower (50%, p < 0.05). The amount of blood purified was higher in survivors than in non-survivors (8.5 ± 4.4 vs. 6.1 ± 3.6 l/kgBW, p = 0.017). We identified three clusters of <6 l/kgBW, 6-13 l/kgBW and ≥ 13 l/kgBW with a linear dose-response relation between blood purification volume and survival, which was best in the highest volume cluster (83.3%; p = 0.045). The application of CytoSorb® seems to be effective in various conditions of septic shock. In a cohort of most severely ill patients the observed mortality was lower than predicted and decreased linearly with blood purification volumes inadvertently exceeding 6 l/kg BW. These results suggest that hemoadsorption might improve survival provided that the applied dose is high enough. [Display omitted] •Excessive cytokine overshoot contributes to mortality in septic shock and severe inflammatory response syndrome•Hemoadsorption with Cytosorb is a new treatment targeting the cytokine storm•The effects of hemoadsorption on mortality are related to the applied dose•The amount of blood purified ≥13 l/kg was associated with better outcome•Hemoadsorption may improve survival provided that the applied dose is high enough

Background The Endotoxin Activity Assay™ (EAA) is a commercially available diagnostic test that quantifies endotoxin activity in human whole blood. Despite its promising features, the clinical utility of the EAA in the management of sepsis remains incompletely understood. This study aims to comprehensively review the published literature on the EAA and explore its usage trends and clinical applications in sepsis management. Methods We conducted a scoping review focused on EAA measurement in human sepsis subjects across four major databases: Embase, Web of Science, MEDLINE, and Cochrane Library. All the studies published from the inception of the databases to the search date in May 2025 were screened. Reviews, editorials, conference abstracts, grey literature, and non-human studies were excluded. We extracted and analyzed cohort characteristics, timing and frequency of EAA measurement, and the reported EAA results. Results Our systematic search and screening identified 95 articles that applied EAA on human patients, 54 of which focused on sepsis. These studies were published between 2002 and 2025 and reported EAA results in adult and pediatric patients. Most studies were conducted in Europe (51.9%), Asia (22.2%), and North America (11.1%). The most common study scenario involved using EAA as an inclusion criterion for blood purification therapy for sepsis, primarily polymyxin-B hemoadsorption. Of the 54 studies, three were randomized controlled trials conducted in North America, Thailand, and Switzerland. These trials investigated the effect of endotoxin adsorption therapy and continuous renal replacement therapy with adsorption filters for septic shock, using EAA ≥ 0.6 as part of the inclusion criteria. Nearly half of the studies (48.1%) measured EAA levels more than twice per patient, suggesting that serial endotoxin monitoring is of clinical interest. Conclusions Our results highlight the clinical application of EAA measurement in sepsis patient populations worldwide, particularly its potential role in the application of blood purification therapy. Together with other biomarkers and further validation studies to establish relevant timing, frequency, and cut-off values for sepsis patients, the EAA has the potential to become a component of precision medicine in the ICU by identifying patient subgroups most likely to benefit from targeted interventions, such as blood purification.

Hemoadsorption with polystyrene-divinylbenzene (PS-DVB)-based adsorbents is explored as an adjunctive extracorporeal therapy in selected critically ill patients with dysregulated systemic inflammation. However, such therapy must not interfere with standard treatments, including antimicrobial therapy and hemodynamic stabilization with vasoactive drugs. As catecholamines are rarely quantified analytically in clinical practice, there are currently no studies reporting actual plasma levels during hemoadsorption. This in vitro study evaluated whether hemoadsorption with PS-DVB-based adsorbents alters plasma concentrations of epinephrine, norepinephrine, and dobutamine. Miniaturized PS-DVB adsorbers were used in 300-minute experiments; serial plasma samples were quantified, and apparent plasma clearance was derived from concentration-time data. Epinephrine and norepinephrine concentrations remained essentially unchanged over 300 min, with very low apparent plasma clearance (< 5 mL/min), indicating no meaningful removal under the tested conditions. By contrast, dobutamine demonstrated consistent, measurable clearance (approximately 5–15 mL/min), indicating non-negligible adsorption. Under these in vitro conditions, PS-DVB hemoadsorption did not materially remove epinephrine or norepinephrine but produced measurable removal of dobutamine. These findings are compatible with observational reports of reduced overall vasopressor requirements during hemoadsorption, while highlighting the potential for dobutamine underexposure. Future clinical studies should directly measure therapeutic plasma levels – particularly for dobutamine – during PS-DVB hemoadsorption and assess whether dosing adjustments are required to maintain intended inotropic effects without compromising safety.

Keywords: Cardiac surgery, Hemoadsorption, Sepsis, Endocarditis, Prolonged bypass time, Endotoxin, oXiris

The “normal” immune response to an insult triggers a highly regulated response determined by the interaction of various immunocompetent cells with pro- and anti-inflammatory cytokines. Under pathologic conditions, the massive elevation of cytokine levels (“cytokine storm”) could not be controlled until the recent development of hemoadsorption devices that are able to extract a variety of different DAMPs, PAMPs, and metabolic products from the blood. CytoSorb® has been approved for adjunctive sepsis therapy since 2011. This review aims to summarize theoretical knowledge, in vitro results, and clinical findings to provide the clinician with pragmatic guidance for daily practice. English-language and peer-reviewed literature identified by a selective literature search in PubMed and published between January 2016 and May 2021 was included. Hemoadsorption can be used successfully as adjunct to a complex therapeutic regimen for various conditions. To the contrary, this nonspecific intervention may potentially worsen patient outcomes in complex immunological processes. CytoSorb® therapy appears to be safe and useful in various diseases (e.g., rhabdomyolysis, liver failure, or intoxications) as well as in septic shock or cytokine release syndrome, although a conclusive assessment of treatment benefit is not possible and no survival benefit has yet been demonstrated in randomized controlled trials.