Extracorporeal Hemoadsorption Research Articles

Prolonged Bactericidal Activity in Extracorporeal Hemoadsorption with Vancomycin-Functionalized HA380 Sorbent Cartridge

Prolonged Bactericidal Activity in Extracorporeal Hemoadsorption with Vancomycin-Functionalized HA380 Sorbent Cartridge

Hemoadsorption therapy for myoglobin removal in rhabdomyolysis: consensus of the hemoadsorption in rhabdomyolysis task force

BackgroundRhabdomyolysis describes a syndrome characterized by muscle necrosis and the subsequent release of creatine kinase and myoglobin into the circulation. Myoglobin elimination with extracorporeal hemoadsorption has been shown to effectively remove myoglobin from the circulation. Our aim was to provide best practice consensus statements developed by the Hemoadsorption in Rhabdomyolysis Task Force (HRTF) regarding the use of hemadsorption for myoglobin elimination.MethodsA systematic literature search was performed until 11th of January 2023, after which the Rhabdomyolysis RTF was assembled comprising international experts from 6 European countries. Online conferences were held between 18th April − 4th September 2023, during which 37 consensus questions were formulated and using the Delphi process, HRTF members voted online on an anonymised platform. In cases of 75 to 90% agreement a second round of voting was performed.ResultsUsing the Delphi process on the 37 questions, strong consensus (> 90% agreement) was achieved in 12, consensus (75 to 90% agreement) in 10, majority (50 to 74%) agreement in 13 and no consensus (< 50% agreement) in 2 cases. The HRTF formulated the following recommendations: (1) Myoglobin contributes to the development of acute kidney injury; (2) Patients with myoglobin levels of > 10,000 ng/ml should be considered for extracorporeal myoglobin removal by hemoadsorption; (3) Hemoadsorption should ideally be started within 24 h of admission; (4) If myoglobin cannot be measured then hemoadsorption may be indicated based on clinical picture and creatinine kinase levels; (5) Cartridges should be replaced every 8–12 h until myoglobin levels < 10,000 ng/ml; (6) In patients with acute kidney injury, hemoadsorption can be discontinued before dialysis is terminated and should be maintained until the myoglobin concentration values are consistently < 5000 ng/ml.ConclusionsThe current consensus of the HRTF support that adjuvant hemoadsorption therapy in severe rhabdomyolysis is both feasible and safe and may be an effective method to reduce elevated circulating levels of myoglobin.

Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP): A single center, open-label, three-arm, randomized, controlled intervention pilot trial.

To investigate the efficacy of bilirubin reduction by hemoadsorption with CytoSorb® in patients with acute-on-chronic liver failure (ACLF) receiving continuous renal replacement therapy (CRRT). A prospective, randomized, single-center, open-label, controlled pilot trial. Patients with ACLF, acute kidney injury, and serum bilirubin ≥5 mg/dL were assigned 1:1:1 to one of three study groups (CRRT with or without hemoadsorption, no CRRT). In the hemoadsorption group, the CytoSorb adsorber was incorporated into the CRRT system, replaced after 12, 24, and 48 h, and removed after 72 h. The primary endpoint was the serum bilirubin level after 72 h. CYTOHEP was terminated early due to difficulties in recruiting patients and ethical concerns. Three of 9 patients (33%) were treated in each group. Comparing the three groups, mean bilirubin levels after 72 h were lower by -8.0 mg/dL in the "CRRT with hemoadsorption" group compared to "CRRT without hemoadsorption" (95% CI, -21.3 to 5.3 mg/dL; p = 0.17). The corresponding mean difference between "CRRT without hemoadsorption" and "no CRRT" was -1.4 mg/dL (95% CI, -14.2 to 11.5 mg/dL; p = 0.78). Comparing "CRRT with hemoadsorption" and "no CRRT," it was -9.4 mg/dL (95% CI, -20.8 to 2.1 mg/dL; p = 0.0854). Only 1/9 patients (11%, "no CRRT" group) survived day 30 after study inclusion but died on day 89. IL-6, liver function parameters, and clinical scores were similar between the study groups. CYTOHEP failed to demonstrate that extracorporeal hemoadsorption combined with CRRT can reduce serum bilirubin in ACLF patients with acute kidney failure.

Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock: An Indian perspective.

Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor. Newer adjuvant therapy, such as CytoSorb® extracorporeal haemoadsorption device, has been investigated and shown promising outcome. However, there is a lack of some guidance to make clinical decisions on the use of CytoSorb® haemoadsorption as an adjuvant therapy in septic shock in Indian Setting. Therefore, this expert consensus was formulated. To formulate/establish specific consensus statements on the use of CytoSorb® haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario. We performed a comprehensive literature on CytoSorb® haemoadsorption in sepsis, septic shock in PubMed selecting papers published between January 2011 and March 2023 2021 in English language. The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps. Using a modified Delphi approach combining evidence appraisal and expert opinion, the following topics related to CytoSorb® in septic shock were addressed: need for adjuvant therapy, initiation timeline, need for Interleukin -6 levels, duration of therapy, change of adsorbers, safety, prerequisite condition, efficacy endpoints and management flowchart. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. All 11 experts in the consensus group (100%) participated in the first, second and third round of voting. After three iterative voting rounds and adapting two statements, consensus was achieved on nine statements out of nine statements. The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb® for all indications in the open-ended question (Q10) focusing on "future recommendations for CytoSorb® therapy". This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb® haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

Use of Anakinra in a Case of Severe Dengue with Refractory Secondary Hemophagocytic Lymphohistiocytosis

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe life-threatening systemic inflammatory syndrome which may be secondary to infections. It is a potential complication of severe dengue. We report a child with severe dengue with worsening clinical course due to secondary HLH. The refractory course responded to intravenous anakinra (an interleukin-1 blocker) as an add-on therapy. Clinical Description: An 11-year-old girl with dengue presented on the 7th day, with progressively worsening clinical condition, having developed multi-organ dysfunction syndrome. Management and Outcome: She required mechanical ventilation, hemodialysis, and extracorporeal hemoadsorption therapy. In view of secondary HLH, intravenous immunoglobulin and methylprednisolone were administered, but there was clinical worsening. Hence, anakinra was initiated and improvement was noted in the next 48 hours. The child was finally extubated on day 17 of illness and could be discharged. Conclusion: Secondary HLH should be considered early in severe dengue cases with cytopenias, hyperferritinemia, and multi-organ dysfunction and immunotherapy should be initiated without delay. Anakinra is a promising, efficient, therapeutic choice and may have a beneficial role and better prognosis if started early in rapidly worsening HLH.

Sorbent functionalization with vancomycin enhances bacteria killing in extracorporeal hemoadsorption.

The level of bacteremia in patients with sepsis and septic shock is a predictor of complications and mortality, regardless of the type of bacteria. Devices for bacteria, endotoxin and cytokines removal by adsorption have been recently developed. Thus, extracorporeal blood purification therapies have been proposed as adjunctive therapy in sepsis in combination with drugs. Some potentially useful drugs, however, are precluded due to their organ or metabolic toxicity. The present study represents a preliminary report on the invitro effect of a sorbent device (minimodule with HA380 beads, Jafron medical, Zhuhai, China) in which the particles have been functionalized with vancomycin on the surface. The impact of the surface-modified beads on circulating bacteria (Staphylococcus aureus) has been tested in a simulated invitro circulation. In vitro experiments were carried out with 800 mL of blood enriched with S. aureus species. Blood was circulated in the vancomycin-functionalized and non-functionalized mini-module cartridges in hemoadsorption setup (300 mL each) and the bactericidal effect was assessed. Also, 200 mL of blood was used as a control. A significant increase in the time to positivity of blood cultures was observed after 60 min and also after 120 min of therapy with the mini-module functionalized with vancomycin as opposed to the non-functionalized cartridge. These results suggest a possible way of treating sepsis by using drug- or antibiotic-functionalized cartridges without worrying about pharmacological toxicity. The prolongation of the time to bacterial culture positivity to S. aureus after a passage through a column packed with beads functionalized with vancomycin represents a proof of concept.

EFFICACY OF SUPPLEMENTAL HEMOADSORPTION THERAPY ON SEVERE AND CRITICAL PATIENTS WITH COVID-19: AN EVIDENCE-BASED ANALYSIS.

Background: The COVID-19 pandemic has posed a disproportionately high threat to the global health system and social stability. COVID-19 damage can lead to hyperinflammation and tissue damage due to a "cytokine storm," which in turn contributes to an increase in the mortality rate. Extracorporeal hemoadsorption therapy (HAT) in patients with severe COVID-19 may improve organ function and stabilize hemodynamic status; however, the effects of supplemental HAT remain controversial. Methods: The Cochrane Library, Embase, and PubMed databases were comprehensively searched from inception to August 20, 2022, for potential studies. Results: A total of 648 patients with severe COVID-19 in three randomized controlled trials and 11 observational studies met the inclusion criteria. A meta-analysis indicated that supplemental HAT significantly improved the mortality rate of patients with severe COVID-19 compared with conventional therapy (relative risk [RR] = 0.74, 95% confidence interval [CI] = 0.56 to 0.96, P = 0.026). In subgroup analyses, supplemental HAT significantly decreased mortality rates in patients without extracorporeal membrane oxygenation (ECMO) support (RR = 0.59, 95% CI = 0.44-0.79, P < 0.0001), while a significant difference was not observed in patients requiring ECMO support (RR = 1.61, 95% CI = 0.63-4.09, P = 0.316). Standardized mean difference (SMD) meta-analysis showed that IL-6 removal was more significant in HAT group than conventional therapy group (SMD = 0.46, 95% CI = 0.01 to 0.91, P = 0.043), followed by C-reactive protein (SMD = 0.70, 95% CI = -0.04 to 1.44, P = 0.065) and IL-8 (SMD = 0.36, 95% CI = -0.34 to 1.07, P = 0.311). No evidence of substantial publication bias concerning mortality was observed. Conclusion: Given the better mortality outcomes, HAT confers clinical benefits to patients with severe COVID-19, which correlated with cytokine removal by HAT. Cytokine adsorption may not provide clinical benefits for patients with severe COVID-19 requiring ECMO and should be used with caution. However, because of the very low quality of evidence, multicenter randomized trials with large sample sizes are required to verify these findings.

Extracorporeal hemoadsorption therapy as a potential therapeutic option for rapid removal of Apixaban in high risk-surgical patients: a case report

BackgroundApixaban is a non-vitamin K antagonist oral anticoagulant (NOACs) recently emerged as an effective alternative to conventional vitamin K antagonists (VKAs) in the treatment of several thromboembolic disorders. However, in case of overdose or in patients requiring emergency surgery there is a high bleeding rate and severe adverse side effects due to the absence of an antidote. There is promising data from in vitro and clinical studies, that certain antithrombotic agents (that is Rivaroxaban and Ticagrelor) have been successfully removed by the extracorporeal hemoadsorption therapy CytoSorb. Here, we present the case of a patient successfully treated with CytoSorb as a kind of antidote to enable emergency surgery for bilateral nephrostomy.Case presentationA 82-year-old Caucasian man was admitted to the Emergency Room with acute kidney injury (AKI) in the context of severe bilateral hydroureteronephrosis. The patient’s medical history included chronic obstructive pulmonary disease, arterial hypertension, atrial fibrillation (anticoagulated with Apixaban) and a locally advanced prostate adenocarcinoma treated with trans-ureteral resection of the bladder and radiotherapy in the previous months. The indication for a bilateral nephrostomy could not be considered immediately given the major bleeding risk due to Apixaban, which was discontinued and replaced with calciparin. After 36 hours of continuous renal replacement therapy (CRRT), the Apixaban blood level was still elevated and it was decided to install CytoSorb into the running CRRT to accelerate the drug clearance. After 2 hours 30 minutes, there was good reduction of Apixaban from 139 to 72 ng/ml (reduction rate of 48.2%) registered, and this allowed for an easy placement of bilateral nephrostomies without complications. Four days after surgery renal function parameters further normalized, the patient did not require additional dialysis treatments and Apixaban therapy was prescribed again once the patient returned home.ConclusionsIn this case we report the findings of a patient with post-renal AKI requiring emergency nephrostomy placement while on chronic anticoagulation with Apixaban therapy. Combined treatment with CRRT and CytoSorb was associated with the rapid and effective removal of Apixaban allowing for prompt and urgent surgery while simultaneously ensuring the low risk of bleeding as well as an uneventful post-operative course.

Extracorporeal hemoadsorption in critically ill COVID-19 patients on VV ECMO: the CytoSorb therapy in COVID-19 (CTC) registry

ObjectivesThe CytoSorb therapy in COVID-19 (CTC) registry evaluated the clinical performance and treatment parameters of extracorporeal hemoadsorption integrated with veno-venous extracorporeal membrane oxygenation (VV ECMO) in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) and respiratory failure under US FDA Emergency Use Authorization.DesignMulticenter, observational, registry (NCT04391920).SettingIntensive care units (ICUs) in five major US academic centers between April 2020 and January 2022.PatientsA total of 100 critically ill adults with COVID-19-related ARDS requiring VV ECMO support, who were treated with extracorporeal hemoadsorption.InterventionsNone.Measurements and main resultsBaseline demographics, clinical characteristics, laboratory values and outcomes were recorded following individual ethics committee approval at each center. Detailed data on organ support utilization parameters and hemoadsorption treatments were also collected. Biomarker data were collected according to the standard practice at each participating site, and available values were compared before and after hemoadsorption. The primary outcome of mortality was evaluated using a time-to-event analysis. A total of 100 patients (63% male; age 44 ± 11 years) were included. Survival rates were 86% at 30 days and 74% at 90 days. Median time from ICU admission to the initiation of hemoadsorption was 87 h and was used to define two post hoc groups: ≤ 87 h (group-early start, GE) and > 87 h (group-late start, GL). After the start of hemoadsorption, patients in the GE versus GL had significantly shorter median duration of mechanical ventilation (7 [2–26] vs. 17 [7–37] days, p = 0.02), ECMO support (13 [8–24] vs. 29 [14–38] days, p = 0.021) and ICU stay (17 [10–40] vs 36 [19–55] days, p = 0.002). Survival at 90 days in GE was 82% compared to 66% in GL (p = 0.14). No device-related adverse events were reported.ConclusionsIn critically ill patients with severe COVID-19-related ARDS treated with the combination of VV-ECMO and hemoadsorption, 90-day survival was 74% and earlier intervention was associated with shorter need for organ support and ICU stay. These results lend support to the concept of “enhanced lung rest” with the combined use of VV-ECMO plus hemoadsorption in patients with ARDS.

Bilirubin Removal by Polymeric Adsorbents for Hyperbilirubinemia Therapy.

Hyperbilirubinemia, presenting as jaundice, is a life-threatening critical illness in newborn babies and acute severe hepatic failure patients. Over the past few decades, extracorporeal hemoadsorption by adsorbent therapy has been widely applied in the treatment of hyperbilirubinemia. The capability of hemoadsorption depends on the adsorbents. Most of the clinically used bilirubin adsorbents are made up of styrene/divinylbenzene copolymer and quaternary ammonium salt, which usually have poor biocompatibility and weak mechanical strength. To overcome the drawbacks of commercial polymer adsorbents, advanced synthetic and natural polymers with/without nanomaterials have been designed, and novel adsorbent fabrication technologies have also been developed. In this review, the adsorption mechanism of bilirubin adsorbents has been summarized, which is the basic criterion in adsorbent development. Furthermore, the preparation method, adsorption mechanism, relative merits and practicability of the emerging bilirubin adsorbents have been evaluated. Based on the existing studies, this work highlights the future direction of the efforts on how to design and develop bilirubin adsorbents with good overall clinical performance. Perhaps this study can change traditional perspectives and propose new strategies for bilirubin clearance from the aspects of pathogenic mechanisms, metabolic pathways, and material-based innovation.

Effect of extracorporeal hemoadsorption in critically ill patients with COVID-19: A narrative review.

COVID-19 has been affecting the world unprecedentedly and will remain widely prevalent due to its elusive pathophysiological mechanism and the continuous emergence of new variants. Critically ill patients with COVID-19 are commonly associated with cytokine storm, multiple organ dysfunction, and high mortality. To date, growing evidence has shown that extracorporeal hemoadsorption can exert its adjuvant effect to standard of care by regulating immune homeostasis, reducing viremia, and decreasing endotoxin activity in critically ill COVID-19 cases. However, the selection of various hemofilters, timing of initiation and termination of hemoadsorption therapy, anticoagulation management of extracorporeal circuits, identification of target subgroups, and ultimate survival benefit remain controversial. The purpose of this narrative review is to comprehensively summarize the rationale for the use of hemoadsorption in critically ill patients with COVID-19 and to gather the latest clinical evidence in this field.

Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: Review of the rationale and current clinical experiences.

Many severe intoxications occur with substances with no specific antidote, which is why methods of extracorporeal elimination represent a particularly useful and even critical component in their management. The purpose of this review is to summarize the accumulating evidence and clinical results from the application of CytoSorb hemoadsorption therapy in patients with severe intoxications. The technology represents a promising technique with an increasing number of publications in a variety of severe intoxication scenarios suggesting that early intervention might provide rapid substance removal with subsequent overall clinical improvement. Given the tremendous challenges in performing prospective, randomized trials in this field, the strong safety profile of the device and the high acuity of these life-threatening situations, CytoSorb should be considered as a therapeutic option in severe intoxications, particularly when direct antidotes are not available. However, further clinical data are desirable to provide precise recommendations.

Survival of Patients Treated With Extracorporeal Hemoadsorption and Extracorporeal Membrane Oxygenation: Results From a Nation-Wide Registry.

Extracorporeal hemoadsorption with the CytoSorb adsorber is increasingly being used during the past years. The use in combination with extracorporeal membrane oxygenation (ECMO) is feasible, but frequency of its use and outcomes have not been assessed in larger cohorts. We analyzed all patients treated with veno-venous (VV) ECMO either with or without CytoSorb in Germany from 2017 to 2019. Data were retrieved from a nationwide claim dataset collected by the Research Data Center of the Federal Bureau of Statistics. During this three-year episode, 7,699 patients were treated with VV ECMO. Among these, the number of CytoSorb-treated patients constantly increased from 156 (6.6%) in 2017 to 299 (11.8%) in 2019. In this large cohort hemoadsorption with the CytoSorb adsorber was associated with higher mortality and increased treatment costs. Due to limited information in the dataset about the severity of disease comparison of outcomes of patients treated with and without CytoSorb has to be interpreted with caution. Further studies have to examine if this finding is due to a negative effect of hemoadsorption with the CytoSorb device or is rather to be attributed to disease severity.

Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta-analysis of randomized controlled trials.

BackgroundThe effects and safety of extracorporeal hemoadsorption with CytoSorb® in critically ill patients with inflammatory conditions are controversial.MethodsWe performed a systematic review with meta‐analysis and trial sequential analysis (TSA) of randomized‐controlled trials to assess the mortality and safety of CytoSorb® therapy in critically ill patients with inflammatory conditions. Electronic databases were searched up to April 2022. The primary outcome was mortality at longest follow‐up and secondary outcomes included various adverse event (AE) outcomes. Conflict of interest and funding of each trial were assessed. We calculated relative risk (RR) and 95% confidence interval (CI).ResultsFourteen published (n = 764) and 4 unpublished (n = 111) trials were included. Eight trials were performed in medical ICU patients and 10 in complex cardiac surgery. Ten trials had significant industrial funding or an author conflict of interest. Hemoadsorption with CytoSorb® was associated with higher mortality at latest follow‐up (16 trials, n = 807, 120 of 402 [29.85%] patients in the CytoSorb® group vs. 98 of 405 [24.20%] patients in the control group, RR = 1.24 [95% CI, 1.04–1.49], p = .02, [TSA‐adjusted CI, 0.92–1.68]) and at 30‐days or in‐hospital (11 trials, n = 727; RR = 1.41 [95% CI, 1.06–1.88], p = .02, [TSA‐adjusted CI, 0.44–4.62]). Only one trial reported the definition of adverse event, while detailed results were reported in 3 trials; the risk of adverse events was not higher with CytoSorb®. Certainty of evidence ranged from low to very low.ConclusionLow certainty of evidence showed that the use of CytoSorb® might increase mortality in critically ill patients with inflammatory conditions. Adverse events were frequent but underreported and not systematically evaluated. Industrial funding and conflict of interest were common. Considerable uncertainty about the findings does not allow firm conclusions and suggests a need for high‐quality randomized trials to clarify mortality and adverse events related to CytoSorb®.Editorial CommentHemoadsorption with CytoSorb® have been used in critically ill patients despite lack of high quality data from RCTs suggesting any patient‐important benefits. The findings from this systematic review and meta‐analysis suggests an increased risk of adverse events including mortality. With no apparent benefits and at the same time risk of harm, use of hemoadsorption with CytoSorb® in daily clinical practice cannot be recommended at this time.

Blood purification therapy in patients with severe COVID-19 requiring veno-venous ECMO therapy: A retrospective study.

Patients with severe manifestations of COVID-19 might exhibit characteristics of a sepsis-like syndrome that can progress to multiple organ failure and ultimately death. Underlying mechanism have been explored and suggest a profound dysregulation of the immune system associated with hyperinflammation, hemodynamic instability and respiratory failure. Besides standard intensive care treatment, approaches modulating the dysregulated immune response, such as CytoSorb hemoadsorption, have been used. However, data of ECMO-dependent patients in comparison to a control cohort remain scarce. Included were 26 critically ill COVID-19 patients requiring high-flow veno-venous extracorporeal membrane oxygenation (high-flow VV ECMO) therapy due to severe acute respiratory distress syndrome (ARDS), of whom 16 were additionally treated with an extracorporeal hemoadsorption device, and compared to a control group of 10 patients. Assessed were levels of inflammatory markers, vasopressor requirements, oxygenation parameters, as well as clinically relevant outcome variables. Data were prospectively recorded and retrospectively analyzed. Treatment with the applied multimodal therapy approach resulted in a stabilization in hemodynamics, a control of the hyperinflammatory response as evidenced by a significant reduction in inflammatory mediators, as well as a marked improvement in lung function. No device related adverse events were observed while treatment appeared safe and feasible. Treatment of a critically ill COVID-19 ARDS patients with combined VV ECMO support and hemoadsorption therapy led to a rapid and sustained hemodynamic stabilization, a control of the uncontrolled inflammatory response and an improvement in oxygenation. Given these signals pointing toward a patient-oriented benefit of extracorporeal hemoadsorption therapy in those patients, future controlled, randomized studies should focus on the investigation of the appropriate timing and dosing of this promising treatment modality.

Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP)\u2014a single center, open-label, three-arm, randomized, controlled intervention trial

BackgroundLiver cirrhosis is a major healthcare problem and the mortality rate is high. During recent years, systemic inflammation has been recognized as a major driver of hepatic decompensation and progression of liver cirrhosis to acute-on-chronic liver failure (ACLF). The aim of the CYTOHEP study is to assess the impact of extracorporeal hemoadsorption with the CytoSorb adsorber on serum bilirubin concentrations, humoral inflammation parameters, liver function parameters, and patient survival in patients with ACLF and acute kidney injury (AKI).MethodsThe CYTOHEP study is a prospective, single-center, open-label, three-arm, randomized, controlled intervention trial. Patients with ACLF and AKI stage 3 according to Kidney Disease: Improving Global Outcome (KDIGO) criteria will be randomized into three groups to be treated with (1) continuous renal replacement therapy (CRRT) and CytoSorb, (2) CRRT without CytoSorb, and (3) without both, CRRT and CytoSorb. In the hemoadsorption group, CytoSorb will be used for 72 h. The other groups receive standard of care with early or late initiation of CRRT, respectively. Primary endpoint of the study is serum bilirubin concentration after 72 h, important secondary endpoints are 30-day survival and a panel of inflammatory parameters.DiscussionThe CYTOHEP study is designed to evaluate the benefit of extracorporeal hemoadsorption in patients with ACLF. The results of this study will help to better understand the potential role of hemoadsorption for the treatment of ACLF and its impact on bilirubin levels, inflammatory parameters, and survival.Trial registrationClinicalTrials.gov NCT05019352. Registered on August 24, 2021. Deutsches Register Klinischer Studien (DRKS) DRKS00026082.

Extracorporeal Cytokine Removal in Critically Ill COVID-19 Patients: A Case Series.

Introduction: Extracorporeal hemoadsorption (HA) is a potential adjunctive therapy in severe cases of COVID-19 associated pneumonia. In this retrospective study we report data from critically ill patients treated with HA during the first and second wave of the pandemic.Patients and Methods: All patients, who received HA therapy with CytoSorb within the first 96 h of intensive care unit (ICU) admission without hospital-acquired bacterial superinfection, were included. Clinical and laboratory data were collected: on admission, before (TB) and after (TA) HA therapy.Results: Out of the 367 COVID-19 cases, 13 patients were treated with CytoSorb, also requiring mechanical ventilation and renal replacement therapy. All patients were alive at the end of HA, but only 3 survived hospital stay. From TB-TA there was a tendency of decreasing norepinephrine requirement: 193.7 [IQR: 34.8–270.4] to 50.2 [6.5–243.5] ug/kg/day and increasing PaO2/FiO2 ratio 127.8 (95% CI: 96.0–159.6) to 155.0 (115.3–194.6) mmHg but they did not reach statistical significance (p = 0.14 and 0.58, respectively). Treatment related adverse events were not reported.Conclusion: The treatment was well-tolerated, and there was a tendency toward an improvement in vasopressor need and oxygenation during the course of HA. These observations render the need for prospective randomized trials.

Opportunities, controversies, and challenges of extracorporeal hemoadsorption with CytoSorb during ECMO.

Extracorporeal membrane oxygenation (ECMO) is frequently used in many centers around the globe for various indications. However, prognosis is often poor even with all supportive therapies, and in many cases, clinical deterioration is associated with inflammation. Hemoadsorption with CytoSorb is a novel approach to limit the inflammatory response, and the device can be safely and easily installed into ECMO circuits. CytoSorb has been used more than 130.000 times to date, but because randomized controlled trials are largely lacking, there is substantial debate on its use. Here, experts from critical care medicine, cardiology, cardiac surgery, and perfusion technology discuss the pros and cons of this novel therapy and outline the future aspects for its clinical application and research.

Adjuvant hemoadsorption therapy in patients with severe COVID-19 and related organ failure requiring CRRT or ECMO therapy: A case series.

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. 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. 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. 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.

Blood purification with CytoSorb in critically ill COVID-19 patients: A case series of 26 patients.

Severe forms of the coronavirus disease 2019 (COVID‐19) can progress to sepsis‐like complications accompanied by “cytokine storm” for which the most effective treatment has not yet been established. Our study describes the results of CytoSorb hemoadsorption in COVID‐19 patients treated on the intensive care unit (ICU). In this retrospective study, 26 patients with COVID‐19 and acute respiratory distress syndrome (ARDS) were treated with hemoadsorption therapy. Pre‐, and post‐treatment values (clinical and laboratory) were compared. Data are expressed as mean (confidence intervals, CI), or median [interquartile ranges, IQR], as appropriate. Patients received 2 hemoadsorption treatments. This resulted in a significant decrease in norepinephrine requirements, and inflammatory marker plasma concentrations (procalcitonin, C‐reactive protein, ferritin) when comparing pre versus post treatment levels. The PaO2/FiO2 and overall organ function (ie, Sequential Organ Failure Assessment—SOFA score) also improved significantly. Patients stayed on the ICU for 9 days and 21 of them survived. To the best of our knowledge, this is one of the largest case series to date reporting early experiences on extracorporeal hemoadsorption therapy in SARS‐CoV‐2 positive patients with hyperinflammation and moderate ARDS. Treatment proved to be effective, technically feasible and well‐tolerated.