The role of hemoadsorption in cardiac surgery - a systematic review.

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.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry.

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.

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

BACKGROUND: Rhabdomyolysis 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. METHODS: A 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. RESULTS: Using 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. CONCLUSIONS: The 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.

Hemoadsorption in Heart Failure Requiring Mechanical Circulatory Support-A Systematic Review and Meta-Analysis.

Background: Left ventricular assist devices (LVAD) and extracorporeal membrane oxygenation (ECMO) are well established therapies in heart failure (HF) management. Their use is generally associated with a sudden increase in inflammatory mediators, which are often already elevated in patients with HF prior to device implantation. An exaggerated release of proinflammatory cytokines is associated with organ dysfunction and increased mortality. Hemoadsorption has been shown to reduce inflammatory mediators during cardiopulmonary bypass. Objective: To investigate the role of hemoadsorption during the management of acute or chronic heart failure with mechanical circulatory support and its impact on survival. Methods: We systematically searched MEDLINE selecting all studies comparing the use of hemoadsorption during LVAD implantation or veno-arterial (v.a.) ECMO therapy. Records were screened by two different investigators. Reports without a control group and duplicates were excluded. Results: Our search delivered six studies. One was randomized and five were retrospective studies, of which three were risk-adjusted. During LVAD implantation, one study showed no difference in mortality but higher incidence of respiratory insufficiency in the hemoadsorption group (54% vs 30%, p = 0.024) and the other study found higher mortality in the hemoadsorption group (33% vs 0%, p = 0.01). During ECMO therapy, three of four studies including the randomized one found no difference in survival or major adverse cardiac events between the hemoadsorption and the control groups. Only one study found lower mortality in the hemoadsorption group (20% vs 60%. p = 0.02). Conclusions: The results of this literature review suggest that the use of hemoadsorption in patients undergoing LVAD implantation might be associated with higher morbidity and mortality. The majority of studies on the use of hemoadsorption during v.a. ECMO therapy showed no effect on mortality or organ dysfunction, while only one small study showed that hemoadsorption was able to reduce mortality. The results are limited by the retrospective nature and the small sample sizes of the majority of the studies included.

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo.

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.

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

OBJECTIVES: The 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. DESIGN: Multicenter, observational, registry (NCT04391920). SETTING: Intensive care units (ICUs) in five major US academic centers between April 2020 and January 2022. PATIENTS: A total of 100 critically ill adults with COVID-19-related ARDS requiring VV ECMO support, who were treated with extracorporeal hemoadsorption. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline 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. CONCLUSIONS: In 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.

Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia.

INTRODUCTION: Hyperbilirubinemia is often the first evidence for any kind of liver disorder and over one-third of all patients in intensive care units (ICU) show elevated bilirubin concentrations. In critically ill patients, high concentrations of serum bilirubin are correlated with a poor outcome. Therapies to lower bilirubin concentrations are often just symptomatically and their effect on the patients' outcome is hardly evaluated. Therefore, this study investigates whether the extracorporeal elimination of bilirubin with the cytokine adsorber CytoSorb® (CS) reduces mortality in patients with hyperbilirubinemia. METHODS: Patients with bilirubin concentrations >10 mg/dL at the ICU were screened for evaluation from 2018 to 2020. Patients with kidney replacement therapy and older than 18 years were included. Patients with continuously decreasing bilirubin concentrations after liver transplantation or other liver support systems (i.e., Molecular Adsorbents Recirculating System [MARS®], Advanced Organ Support [ADVOS]) were excluded. CS therapy was used in clinical routine and was indicated by the treating physicians. Statistical analysis was performed with IBM SPSS statistics utilizing a multivariate model. Primary outcome measure was the effect of CS on the 30-day mortality. RESULTS: Data from 82 patients (mean Simplified Acute Physiology Score [SAPS] II: 74 points, mean bilirubin: 18 mg/dL, mean lactate: 3.7 mmol/L) were analyzed. There were no significant differences in patients with and without CS treatment. The multivariate model showed no significant effect of CS therapy (p = 0.402) on the 30-day mortality. In addition, a significant effect of bilirubin concentration (p = 0.274) or Model for End-Stage Liver Disease score (p = 0.928) on the 30-day mortality could not be shown. In contrast, lactate concentration (p = 0.001, b = 0.044) and SAPS II (p = 0.025, b = 0.008) had significant impact on 30-day mortality. CONCLUSION: The use of CS in patients with hyperbilirubinemia did not result in a significant reduction in 30-day mortality. Randomized and controlled studies with mortality as primary outcome measure are needed in the future to justify their use.

Successful use of extracorporeal life support and hemadsorption in the context of venlafaxine intoxication requiring cardiopulmonary resuscitation: a case report.

Venlafaxine is a serotonin and noradrenalin reuptake inhibitor prescribed as an antidepressant. Overdose clinically manifests with neurological, cardiovascular and gastrointestinal abnormalities based on, amongst others, serotonin syndrome and can be life-threatening due to cardiovascular collapse. Besides immediate decontamination via gastric lavage and inhibition of enteral absorption through active charcoal, successful hemadsorption with CytoSorb® has been reported. We present the case of a 17-year-old female who required extracorporeal life support (ECLS) for cardiovascular collapse as a result of life-threatening venlafaxine intoxication. Serial serum blood concentrations of venlafaxine/desmethylvenlafaxine on admission at a tertiary hospital (approx. 24 h after ingestion) and subsequently 6 h and 18 h thereafter, as well as on days 2 and 4, were measured. CytoSorb® was initiated 6 h after admission and changed three times over 72 h. The initial blood concentration of venlafaxine/desmethylvenlafaxine was 53.52 µmol/l. After 6 h, it declined to 30.7 µmol/l and CytoSorb® was initiated at this point. After 12 h of hemadsorption, the blood level decreased to 9.6 µmol/l. On day 2, it was down to 7.17 µmol/l and decreased further to 3.74 µmol/l. Additional continuous renal replacement therapy using CVVHD was implemented on day 5. The combination of hemadsorption, besides traditional decontamination strategies along maximal organ supportive therapy with ECLS, resulted in the intact neurological survival of the highest venlafaxine intoxication reported in the literature to date. Hemadsorption with CytoSorb® might help to reduce blood serum levels of venlafaxine. Swift clearance of toxic blood levels may support cardiovascular recovery after life-threatening intoxications.

The effect of cytosorb® application on kidney recovery in critically ill patients with severe rhabdomyolysis: a propensity score matching analysis.

Severe rhabdomyolysis frequently results in acute kidney injury (AKI) due to myoglobin accumulation with the need of kidney replacement therapy (KRT). The present study investigated whether the application of Cytosorb® (CS) led to an increased rate of kidney recovery in patients with KRT due to severe rhabdomyolysis. Adult patients with a myoglobin-concentration >10,000 ng/ml and KRT were included from 2014 to 2021. Exclusion criteria were chronic kidney disease and CS-treatment before study inclusion. Groups 1 and 2 were defined as KRT with and without CS, respectively. The primary outcome parameter was independence from KRT after 30 days. Propensity score (PS) matching was performed (predictors: myoglobin, SAPS-II, and age), and the chi2-test was used. 35 pairings could be matched (mean age: 57 vs. 56 years; mean myoglobin: 27,218 vs. 26,872 ng/ml; mean SAPS-II: 77 vs. 76). The probability of kidney recovery was significantly (p = .04) higher in group 1 (31.4 vs. 11.4%, mean difference: 20.0%, odds ratio (OR): 3.6). Considering patients who survived 30 days, kidney recovery was also significantly (p = .03) higher in patients treated with CS (61.1 vs. 23.5%, mean difference: 37.6%, OR: 5.1). In conclusion, the use of CS might positively affect renal recovery in patients with severe rhabdomyolysis. A prospective randomized controlled trial is needed to confirm this hypothesis.

Post VV-ECMO Weaning Hyperinflammation-Can Prophylactic Hemoadsorption Treatment Prevent Complications?

Acute respiratory distress syndrome (ARDS) is a severe clinical condition characterized by acute respiratory failure and a high mortality risk despite conventional mechanical ventilatory support. Veno-venous extracorporeal membrane oxygenation (vvECMO) has emerged as an effective life-support technology for patients with ARDS. However, complications may arise following the decannulation of vvECMO, with a relatively frequent development of systemic hyperinflammation (SHI). Among the various treatment strategies for SHI, the use of hemoadsorption with CytoSorb® has shown promising results in removing excessive levels of cytokines and attenuating the hyperinflammatory response. In this case series, we present three critically ill patients with ARDS secondary to pneumonia who underwent vvECMO and subsequently received prophylactic hemoadsorption with CytoSorb® following decannulation as a part of our clinical practice. This case series aims to describe the potential positive effects of hemoadsorption in preventing the development of SHI after vvECMO decannulation in ARDS patients.