Extracorporeal Cytokine Adsorption Research Articles

Hemoperfusion with CytoSorb® in Pediatric Patients: A Monocentric Case Series.

Background: Pro- and anti-inflammatory cytokines help regulate the inflammatory response. A cytokine storm is a dysregulated cytokine response associated with sepsis and other conditions that result in a hyper-inflammatory state. Extracorporeal cytokine adsorption has the potential to restore a balanced inflammatory response. Hemoperfusion with CytoSorb® (CS) appears to be a short-term mode of treatment of sepsis in both adults and children. Objective: We present a case series of eight critically ill children involving the use of hemoperfusion with CS at the University Medical Center Ljubljana to treat clinically manifested cytokine storm. Results: In our preliminary experience, it was applied without complication in five children weighing more than 10 kg, who all survived. The effect of age on complications regarding CS treatment is unclear, yet in our case series, all three patients weighing less than 10 kg died of their disease. Conclusions: In our preliminary experience, cytokine adsorption with CS remains a potential adjunctive treatment for cytokine storm in critically ill children.

Extracorporeal cytokine adsorption as therapeutic option for immune effector cell-associated neurotoxicity syndrome.

With the rising number of patients receiving chimeric antigen receptor T-cells, the treatment of this therapy's complications is of growing concern to intensivists and neurologists. We used extracorporeal cytokine adsorption as an add-on therapy in a patient suffering from immune effector cell-associated neurotoxicity syndrome. Interleukin-6 level, which as a readily available parameter is generally used to evaluate course of disease, was rapidly reduced using this method. The patient made a full recovery and is still in hematological remission.

Hemadsorption extracorporeal therapy removes cytokines ex vivo in horses.

Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis. 8 horses owned by North Carolina State University. Four liters of heparinized whole blood was collected from healthy adult horses (n = 8) and stimulated with lipopolysaccharide (100 ng/mL) for 6 hours (37 °C.) from June 4, 2023, to December 15, 2023. Plasma was filtered through a cytokine adsorption device or sham circuit. Samples were collected at 11 time points for multiplex cytokine analysis. Chemistry analysis was performed before and after filtration. To investigate the impact of the device on medication concentrations, equine plasma containing potassium penicillin, gentamicin, and flunixin meglumine was filtered through the cytokine adsorption device or sham for 6 hours. Drug concentrations before and after filtration were determined by ultra-high-performance liquid chromatography. Prefiltration versus postfiltration sample concentrations were analyzed by Student paired t test using GraphPad Prism 9.0 (P < .05). Filtration of lipopolysaccharide-stimulated equine plasma (n = 8) for 6 hours resulted in significant mean reductions in the cytokines IL-10, IL-5, IL-8, tumor necrosis factor-α (TNF-α), and IL-1β, as well as albumin. Drug concentrations of potassium penicillin, gentamicin, and flunixin meglumine were also significantly reduced by filtration. This work provides proof of concept for further investigation of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis.

A matched case-control study on the effectiveness of extracorporeal cytokine adsorption in critically ill patients

Extracorporeal cytokine adsorption aims to reduce cytokine levels in critically ill patients. However, little convincing data exist to support its widespread use. This retrospective study compared interleukin-6 (IL-6) levels in patients treated with or without cytokine adsorber (CytoSorb®). Intensive care patients between Jan 2017 and Dec 2021 who had at least two IL-6 measurements were included. They were divided into an adsorber group and a standard of care group. We screened 3865 patients and included 52 patients in the adsorber group and 94 patients in the standard of care group. Matching was performed and the groups were compared regarding IL-6, lactate, CRP, procalcitonin, vasopressor requirement, and mortality rate. After matching, there were 21 patients in each group. Patients had similar age, ECMO and renal replacement therapy use, baseline noradrenaline requirement, serum lactate, pH, CRP, and IL-6 levels. There were no significant differences in the time course of IL-6, lactate, CRP, procalcitonin and noradrenaline requirement between groups. Two-day and ICU mortality and Kaplan-Meier estimated survival were also comparable. In this matched case-control study no difference in IL-6, inflammatory parameters, noradrenaline requirement or mortality was observed between patients treated with adsorber or standard of care.

Extracorporeal cytokine adsorption reduces systemic cytokine storm and improves graft function in lung transplantation

ObjectivesIschemia–reperfusion injury often coincides with a cytokine storm, which can result in primary graft dysfunction following lung transplantation. Our previous research has demonstrated allograft improvement by cytokine adsorption during ex vivo lung perfusion. The aim of this study was to investigate the effect of in vivo extracorporeal cytokine adsorption in a large animal model. Materials and MethodsPig left lung transplantation was performed following 24 hours of cold ischemic storage. Observation period after transplantation was 24 hours. In the treatment group (n = 6), extracorporeal CytoSorb adsorption was started 30 minutes before reperfusion and continued for 6 hours. A control group (n = 3) did not receive adsorber treatment. ResultsDuring adsorption, we consistently noticed a significant decrease in plasma proinflammatory interleukin (IL)-2, trends of less proinflammatory, tumor necrosis factor- α, IL-1α, and granulocyte-macrophage colony-stimulating factor as well as significantly reduced systemic neutrophils. In addition, a significantly lower peak airway pressure was detected during the 6 hours of adsorption. After 24 hours of observation, when evaluating the left lung allograft independently, we observed significantly improved CO2 removal, partial pressure of oxygen/inspired oxygen fraction ratio, and less acidosis in the treatment group. At autopsy, bronchoalveolar lavage results exhibited significantly lower recruitment of cells and less pro-inflammatory IL-1α, IL-1β, IL-6, and IL-8 in the treatment group. Histologically, the treatment group had a strong trend, indicating less neutrophil invasion into the alveolar space. ConclusionsBased on our findings, cytokine adsorption during and after reperfusion is a viable approach to reducing posttransplant inflammation following lung transplantation. CytoSorb may increase the acceptance of extended criteria donor lungs, which are more susceptible to ischemia–reperfusion injury.

Evaluation of clinical features and laboratory findings in critical intensive care unit patients with severe coronavirus disease-19 who underwent extracorporeal cytokine adsorption.

To evaluate the inflammatory parameters and oxygenation in severe coronavirus disease-19 patients who underwent extracorporeal cytokine adsorption (CA). Patients who underwent extracorporeal CA for cytokine storm were included in the study. The changes in oxygenation, laboratory parameters, and mortality rates were investigated. Thirty-six patients were included in the study. The hemoglobin, thrombocyte, and C-reactive protein (CRP) decreased, and PaO2 /FiO2 ratio increased (p < 0.001; p < 0.01; p < 0.001; p = 0.04, respectively). Twelve (33.3%) patients received a single session, 24 (66.6%) received 2 or more sessions. CRP and fibrinogen levels decreased, and PaO2 /FIO2 ratio increased in the single session group (p = 0.04; p = 0.04; p = 0.01, respectively). In the multi-session group, the hemoglobin, platelet, procalcitonin, and CRP levels decreased, and PaO2 /FIO2 ratio increased (p < 0.01; p = 0.02; p = 0.02; p < 0.01; p = 0.01, respectively). Day 15, 30, and 90 mortality rates were 61.1%, 83.3%, and 88.9%. CA with hemoperfusion reduced CRP and improved oxygenation; however, mortality rates were high.

Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: Results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study.

Outcome of severe acute pancreatitis (SAP) highly depends on the degree of systemic inflammation and organ failure. Although treatment approaches targeting the inflammatory cascade have failed in pancreatitis, recent studies suggest that extracorporeal cytokine adsorption effectively reduces concentrations of pro-inflammatory cytokines and potentially improves the outcome of sepsis. Sixteen patients with SAP, presenting within 7days upon onset of pain, an APACHE-II score of ≥10 and ≥1 marker of poor prognosis, received 2 consecutive 24-h treatments with CytoSorb® extracorporeal cytokine adsorption (intervention group). Hemodynamics, organ failure, and mortality were compared with an APACHE-II score-matched retrospective control group of 32 patients. The primary objective (20% decrease in the vasopressor dependency index or 20% increase in the cardiac index) was reached in 68.8% of the intervention and 28.1% of the control patients (p=0.007), respectively. The cytokine adsorption significantly reduced IL-6 (-1998pg/ml, p=0.005) serum levels and resulted in stable CRP (p=0.101) and decreased PCT (p=0.003) levels in contrast to increased CRP (p=0.014) and stable PCT levels (p=0.695) in the control group. While mortality and improvement of respiratory failure were similar in both groups, renal failure significantly improved (change of KDIGO classification 72h postcytokine adsorption [-1 vs. 0, p=0.005]) and the SOFA score significantly decreased (day 5: -1.8±2.0 vs. 1±3.8, p=0.013) in the intervention group. Cytokine adsorption might be an effective treatment option to stabilize hemodynamics in SAP. It decreases levels of the pro-inflammatory marker IL-6 and stabilizes organ function according to serial SOFA score assessments.

OP164 Extracorporeal Cytokine Adsorption Therapy: An Update Systematic Review Of Clinical Efficacy And Safety For Two Indications

IntroductionThe idea of using extracorporeal cytokine adsorption therapy (ECAT) is to remove cytokines from the blood in order to restore a balanced immune response. Yet, it is unclear as to whether the use of ECAT improves patient-relevant outcomes. Hence, the aim of this article is to synthesize the currently available evidence with regard to a potential clinical benefit of ECAT used in cardiac surgery or sepsis.MethodsWe conducted an updated systematic review summarizing the body of evidence with regard to a potential clinical benefit of ECAT. The study followed the PRISMA statement and the European Network for Health Technology Assessment (EUnetHTA) guidelines. The quality of the individual studies and the strength of the available evidence was assessed using the Cochrane risk of bias tool (v.1) and the GRADE approach respectively. Mortality, organ function, length of stay in the intensive care unit and length of hospitalization, as well as adverse events, were defined as critical outcomes.ResultsFor the preventive treatment of ECAT in patients undergoing cardiac surgery, we found very low-quality inconclusive evidence for mortality (5 randomized controlled trials (RCTs), n = 163), length of stay in the intensive care unit (5 RCTs, n = 163), and length of hospitalization (3 RCTs, n = 101). In addition, very low-quality inconclusive evidence was found for (serious) adverse events (4 RCTs, n = 148). For the therapeutic treatment of ECAT in patients with sepsis/ septic shock, we found very low-quality inconclusive evidence for mortality up to 60-day follow-up (2 RCTs, n = 117), organ function (2 RCTs, n = 117) and length of stay in the intensive care unit (1 study, n = 20). Similarly, very low-quality inconclusive evidence was found for (serious) adverse events (2 RCTs, n = 117). There are currently eighteen ongoing RCTs on the use of ECAT.ConclusionsThere is a lack of reliable data on the clinical benefit of using ECAT as an add-on treatment preventively in cardiac surgery and therapeutically in patients with sepsis or septic shock. While theoretical advantages are anticipated, the current available evidence is inconclusive and was not able to establish the efficacy and safety of ECAT in combination with standard care in the investigated indications. In light of the available RCTs, we strongly recommend the consideration of studies with patient-relevant endpoints and adequate statistical power, instead of investing further research funds on small studies that may not shed more light onto the potential clinical benefit of ECAT. The results of ongoing RCTs are awaited to guide the decision on whether further research funds should be invested in ECAT research or to conclude that the intervention may not show clinical benefits for patients.

Extracorporeal Cytokine Adsorption Therapy As a Preventive Measure in Cardiac Surgery and As a Therapeutic Add-On Treatment in Sepsis: An Updated Systematic Review of Comparative Efficacy and Safety.

Evaluating whether there is a clinical benefit of using extracorporeal cytokine adsorption therapy in two indications. Systematic review. Search on four databases, Medline, Embase, The Cochrane Library, and the European Network for Health Technology Assessment planned and ongoing projects database. Patients with sepsis/septic shock; patients undergoing cardiac surgery. Cytokine adsorption. Randomized controlled trials and prospective studies with concurrent control were eligible for the evidence synthesis. The quality of the individual studies and the strength of the available evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach, respectively. For the preventive treatment of extracorporeal cytokine adsorption therapy in patients undergoing cardiac surgery, we found very low-quality inconclusive evidence for mortality (five randomized controlled trials, n = 163), length of stay in the ICU (five randomized controlled trials, n = 163), and length of hospitalization (three randomized controlled trials, n = 101). Very low-quality inconclusive evidence was found for (serious) adverse events (four randomized controlled trials, n = 148). For the therapeutic treatment of extracorporeal cytokine adsorption therapy in patients with sepsis/septic shock, we found very low-quality inconclusive evidence for mortality up to 60-day follow-up (two randomized controlled trials, n = 117), organ function (two randomized controlled trials, n = 117) and length of stay in the ICU (one randomized controlled trial, n = 20). Very low-quality inconclusive evidence was found for (serious) adverse events (two randomized controlled trials, n = 117). Given the available evidence, the efficacy and safety of extracorporeal cytokine adsorption therapy in combination with standard care in the investigated indications was not established. We strongly recommend considering well-powered studies with patient-relevant endpoints instead of investing further research funds on studies that may not shed light on the clinical benefit of extracorporeal cytokine adsorption therapy.

Effect of Cytokine Adsorption on Survival and Circulatory Stabilization in Patients Receiving Extracorporeal Cardiopulmonary Resuscitation.

Even after the introduction of extracorporeal cardiopulmonary resuscitation (ECPR), survival after cardiac arrest remains poor. Excess release of vasoactive cytokines may be a reason for cardiovascular instability and death after ECPR. Recently, an extracorporeal cytokine adsorption device (CytoSorb) to reduce elevated levels of circulating cytokines has been introduced. So far, it remains unclear if this device may improve survival and cardiovascular stabilization after ECPR. We report data from our investigator-initiated, single-center ECPR registry. We compared 23 ECPR patients treated with cytokine adsorption with a propensity-matched cohort of ECPR patients without cytokine adsorption. We analyzed survival, lactate clearance, vasopressor need, and fluid demand in both groups and performed between-group comparisons. Survival to discharge from intensive care unit (ICU) was 17.4% (4/23) in the cytokine adsorption group and 21.7% in the control group (5/23, P > 0.99). In both groups, we observed a decrease of serum-lactate, need for vasopressors, and fluid demand during the first 72 hours after ECPR. However, in direct comparison, we did not find significant between-group differences. In this retrospective registry study employing propensity score matching, cytokine adsorption in severely ill patients after ECPR was not associated with improved ICU survival nor a decrease of lactate, fluid, or vasopressor levels. Due to small case numbers and the retrospective design of the study, our results neither disprove nor confirm a clinically relevant treatment effect of cytokine adsorption. Results from larger trials, preferably randomized-controlled trials are required to better understand the clinical benefit of cytokine adsorption after ECPR.

Extracorporeal cytokine adsorption: Significant reduction of catecholamine requirement in patients with AKI and septic shock after cardiac surgery.

BackgroundExtracorporeal cytokine adsorption is an option in septic shock as an additional measure to treat a pathological immune response. Purpose of this study was to investigate the effects of extracorporeal cytokine adsorption on hemodynamic parameters in patients with acute kidney injury (AKI) on continuous renal replacement therapy (CRRT) and septic shock after cardiac surgery.MethodsIn this retrospective study, a total of 98 patients were evaluated. Hemoadsorption was performed by the CytoSorb® adsorber. In all patients cytokine adsorption was applied for at least 15 hours and at least one adsorber was used per patient. To compare cumulative inotrope need in order to maintain a mean arterial pressure (MAP) of ≥ 65 mmHg, we applied vasoactive score (VAS) for each patient before and after cytokine adsorption. A paired t-test has been performed to determine statistical significance.ResultsBefore cytokine adsorption the mean VAS was 56.7 points. This was statistically significant decreased after cytokine adsorption (27.7 points, p< 0.0001). Before cytokine adsorption, the mean noradrenalin dose to reach a MAP of ≥ 65 mmHg was 0.49 μg/kg bw/min, the mean adrenalin dose was 0.12 μg/kg bw/min. After cytokine adsorption, significantly reduced catecholamine doses were necessary to maintain a MAP of ≥ 65 mmHg (0.24 μg/kg bw/min noradrenalin; p< 0.0001 and 0.07 μg/kg bw/min adrenalin; p < 0.0001). Moreover, there was a significant reduction of serum lactate levels after treatment (p< 0.0001). The mean SOFA-score for these patients with septic shock and AKI before cytokine adsorption was 16.7 points, the mean APACHE II-score was 30.2 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.7 points was 77,0%, respectively 73,0% on APACHE II-score, while the all-cause in-hospital mortality rate of the patients in this study was 59.2%.ConclusionIn patients with septic shock and AKI undergoing cardiac surgery, extracorporeal cytokine adsorption could significantly lower the need for postoperative inotropes. Additionally, observed versus SOFA- and APACHE II-score predicted in-hospital mortality rate was decreased.

Multicentered prospective investigator initiated study to evaluate the clinical outcomes with extracorporeal cytokine adsorption device (CytoSorb®) in patients with sepsis and septic shock.

BACKGROUNDSepsis is a severe clinical syndrome related to the host response to infection. The severity of infections is due to an activation cascade that will lead to an auto amplifying cytokine production: The cytokine storm. Hemoadsorption by CytoSorb® therapy is a new technology that helps to address the cytokine storm and to regain control over various inflammatory conditions. AIMTo evaluate prospectively CytoSorb® therapy used as an adjunctive therapy along with standard of care in septic patients admitted to intensive care unit (ICU). METHODSThis was a prospective, real time, investigator initiated, observational multicenter study conducted in patients admitted to the ICU with sepsis and septic shock. The improvement of mean arterial pressure and reduction of vasopressor needs were evaluated as primary outcome. The change in laboratory parameters, sepsis scores [acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA)] and vital parameters were considered as secondary outcome. The outcomes were also evaluated in the survivor and non-survivor group. Descriptive statistics were used; a P value < 0.05 was considered to be statistically significant.RESULTSOverall, 45 patients aged ≥ 18 and ≤ 80 years were included; the majority were men (n = 31; 69.0%), with mean age 47.16 ± 14.11 years. Post CytoSorb® therapy, 26 patients survived and 3 patients were lost to follow-up. In the survivor group, the percentage dose reduction in vasopressor was norepinephrine (51.4%), epinephrine (69.4%) and vasopressin (13.9%). A reduction in interleukin-6 levels (52.3%) was observed in the survivor group. Platelet count improved to 30.1% (P = 0.2938), and total lung capacity count significantly reduced by 33% (P < 0.0001). Serum creatinine and serum lactate were reduced by 33.3% (P = 0.0190) and 39.4% (P = 0.0120), respectively. The mean APACHE II score was 25.46 ± 2.91 and SOFA scores was 12.90 ± 4.02 before initiation of CytoSorb® therapy, and they were reduced significantly post therapy (APACHE II 20.1 ± 2.47; P < 0.0001 and SOFA 9.04 ± 3.00; P = 0.0003) in the survivor group. The predicted mortality in our patient population before CytoSorb® therapy was 56.5%, and it was reduced to 48.8% (actual mortality) after CytoSorb® therapy. We reported 75% survival rate in patients given treatment in < 24 h of ICU admission and 68% survival rates in patients given treatment within 24-48 h of ICU admission. In the survivor group, the average number of days spent in the ICU was 4.44 ± 1.66 d; while in the non-survivor group, the average number of days spent in ICU was 8.5 ± 15.9 d. CytoSorb® therapy was safe and well tolerated with no adverse events reported. CONCLUSIONCytoSorb® might be an effective adjuvant therapy in stabilizing sepsis and septic shock patients. However, it is advisable to start the therapy at an early stage (preferably within 24 h after onset of septic shock).

Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation: protocol for a randomised, controlled, open-label intervention, multicentre trial

IntroductionVeno-venous extracorporeal membrane oxygenation (V-V ECMO) is a last resort treatment option in patients with severe COVID-19 related acute respiratory distress syndrome (ARDS). Mortality in these critically ill patients is...

P1065EXTRACORPOREAL CYTOKINE ADSORPTION IN PATIENTS WITH AKI AND SEPTIC SHOCK AFTER CARDIAC SURGERY

Abstract Background and Aims Extracorporeal cytokine adsorption is a new option in septic shock as an additional measure to prevent severe cytokinaemia. The purpose of this study was to investigate the effects of extracorporeal cytokine adsorption on hemodynamics in patients with acute kidney injury (AKI) and septic shock after cardiac surgery. Method In this retrospective study 64 patients with AKI and septic shock after cardiac surgery were investigated for the effect of extracorporeal cytokine adsorption by CytoSorb® columns on hemodynamics. In all patients CytoSorb®-treatment was applied in addition to continuous renal replacement therapy (CRRT) with citrate anticoagulation. A paired t-test has been performed to determine statistical significance. Results Before treatment, the mean noradrenalin dose to reach a mean arterial pressure (MAP) &amp;gt; 65 mmHg was 0.49 µg/kg bw/min, the mean adrenalin dose was 0.1 µg/kg bw/min. 24 h after treatment, significantly reduced catecholamine doses were necessary to maintain a MAP &amp;gt; 65 mmHg (0.23 µg/kg bw/min noradrenalin; p***&amp;lt; 0.0002 and 0.06 µg/kg bw/min adrenalin; p* &amp;lt; 0.02). The mean SOFA-score for these patients with AKI and septic shock 24 h before CytoSorb®- treatment was 16.6 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.6 points was 77 % while the all-cause mortality rate of the patients in this study was 59.4 %. Conclusion In patients with AKI and septic shock after cardiac surgery, 24 h after extracorporeal cytokine adsorption by CytoSorb® the catecholamine dose required to maintain a MAP &amp;gt; 65 mmHg was halved. Additionally, observed in-hospital mortality was lower than SOFA-score predicted mortality.

Extracorporeal cytokine removal in severe CAR-T cell associated cytokine release syndrome

PurposeLife-threatening complications of CD-19 Chimeric antigen receptor - T (CAR-T) cells such as the cytokine release syndrome (CRS)) have been reported. Treatment is limited to IL-6 blockade and steroids although global removal of elevated soluble inflammatory factors might be more effective. MethodsClinical course of a CRS patient treated with extracorporeal cytokine adsorption (Cytosorb®). A panel of 48 cytokines, chemokines and endothelial markers has been analyzed longitudinally. Ex vivo stimulation of endothelial cells to visualize (immunocytochemistry) and quantify (ECIS, TER) endothelial barrier effects. ResultsFollowing CAR-T cell application a 65 years old male developed grade 4 CRS with refractory shock (3 vasopressors) and severe capillary leakage (+37 L/24 h resuscitation). Treatment included IL-6 blockade, methylprednisolone and additionally Cytosorb hemoperfusion. While multiple soluble inflammatory factors were elevated and most of them decreased by more than 50% following Cytosorb, markers of endothelial injury increased steadily (e.g. Angpt-2/Angpt-1) leading to profound endothelial activation and leakage in ex vivo assays. ConclusionThis is the first reported use of cytokine adsorption for CRS showing efficacy in absorption of various cytokines but not endothelial growth factors. A randomized controlled trial to evaluate additional Cytosorb treatment in CRS is currently recruiting at our institution (NCT04048434).

Hemoadsorption by extracorporeal cytokine adsorption therapy (CytoSorb®) in the management of septic shock: A retrospective observational study.

Sepsis results in immunologic disturbances with the release of various inflammatory mediators such as cytokines. Cytokines can damage the cells, and the continuous release of inflammatory mediators leads to severely impaired immunity. Therefore, the reduction in cytokine levels by hemoadsorption represents a new concept for blood purification. CytoSorb® as a hemoadsorption device is a detoxification system, which aims to decrease the cytokines levels. This study was conducted to understand any beneficial effects of CytoSorb® therapy in septic patients. This was a retrospective and observational study, approved by the scientific and ethics committee of Max Super Specialty Hospital, Patparganj, Delhi, India and conducted in compliance with current International Council for Harmonization, Good Clinical Practice, Schedule Y, and Indian Council of Medical Research guidelines. Subjects of either gender (age > 18 year) were included in the study. The data were presented as mean ± standard deviation and categorical as frequency and percentage (%). A p value less than 0.05 (p < 0.05) was considered to be statistically significant. A total number of 36 patients were included in the study. Majority of the patients were male with mean age (56.36 ± 14.83). After therapy, procalcitonin and total leucocyte count levels decreased within 24 h. Post therapy, sepsis-related organ failure assessment (SOFA) score of Day (D)1, D2, and D3 reduced to 10.4 ± 3.63, 8.7 ± 4.02, and 7.8 ± 3.67, respectively. The Acute Physiology and Chronic Health Evaluation (APACHE) II score and predicted mortality were lower in the survivor group as compared to the non-survivor group. Hemoadsorption using the extracorporeal adsorption device (CytoSorb®) might be an effective rescue therapy in stabilizing septic shock patients.

Extracorporeal Cytokine Adsorption as Additive Treatment of CAR-T Associated Cytokine Release Syndrome (CRS)

Extracorporeal Cytokine Adsorption as Additive Treatment of CAR-T Associated Cytokine Release Syndrome (CRS)

Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study

BackgroundThe 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. Methods20 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. ResultsOverall 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. ConclusionsThis 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.

Clinical experience of using a novel extracorporeal cytokine adsorption column for treatment of septic shock with multi organ failure

Clinical experience of using a novel extracorporeal cytokine adsorption column for treatment of septic shock with multi organ failure

Clinical experience of using a novel extracorporeal cytokine adsorption column for treatment of septic shock with multiorgan failure

Severe sepsis and multiorgan failure (MOF) are major causes of death in the ICU. The extracorporeal cytokine adsorption column (ECAC; Cytosorb®, CytoSorbents Corporation, USA), a critical care focused therapeutic device, results in rapid in vitro and in vivo elimination of several key cytokines and prevents organ failure. Use of ECAC in patients with sepsis is a new area of research with insufficient data to promote large prospective RCTs. Studies published to date have shown promising results. We report our clinical experience with ECAC for severe sepsis/septic shock/MOF patients.