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Background Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery. Methods We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care ( n  = 15) or CytoSorb® HA ( n  = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors’ activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII). Results Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors’ adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes. Conclusions CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts. Trial registration ClinicalTrials.gov NCT02775123 . Registered 17 May 2016.

Background Cardiopulmonary bypass (CPB) triggers marked cytokine release often followed by a systemic inflammatory response syndrome, associated with adverse postoperative outcomes. This trial investigates the intraoperative use of haemoadsorption (HA) during cardiac surgery with CPB to assess its impact on postoperative systemic inflammatory response. Methods In this prospective randomised controlled trial (ethics approval no. 5094-14DRKS00007928), patients (> 65 years) undergoing elective on-pump cardiac surgery were randomised to intraoperative HA (CytoSorb) during CPB or standard care without HA. Primary outcome was the difference in mean interleukin (IL)-6 serum concentrations between groups on intensive care unit (ICU) admission. The secondary outcomes included various clinical and biochemical endpoints. Statistical methods included paired and unpaired t-tests, Wilcoxon, Mann–Whitney U-tests, and chi-square tests. Results Thirty-eight patients were allocated to receive either intraoperative HA (n = 19) or standard care (n = 19). The primary outcome, IL-6 levels on ICU admission, did not differ between the study group and controls (214.4 ± 328.8 vs. 155.8 ± 159.6 pg/ml, p  = 0.511). During surgery pre- versus post-adsorber IL-2, IL-6, IL-8, IL-10, heparan sulfate and myoglobin post- levels were reduced. Furthermore, IL-6 levels did not differ between the study groups on day 1 and 2 in the ICU. While sequential organ failure assessment scores, lactate levels, and C-reactive protein and procalcitonin (PCT) showed no statistically significant differences. Regarding haemodynamic stability in the treatment group the cardiac index (3.2 ± 0.7 vs. 2.47 ± 0.47 l/min/m 2 , p  = 0.012) on ICU day 2 increased, and lower fluid requirements as well as decreased fibrinogen requirement were observed. Need for renal replacement therapy did not differ though a shorter duration was observed in the treatment group. Time on ventilator, respiratory parameters, infectious complications, delirium scores, ICU and hospital lengths of stay, and mortality did not differ between groups. Conclusion HA did not reduce the IL-6 level on ICU admission or afterwards. Even though HA reduced cytokine load during cardiac surgery in the treatment group. There were no significant differences between groups in the postoperative course of other cytokine concentrations, organ dysfunction, ICU and hospital lengths of stay and mortality rates. Trial registration prospectively DRKS00007928 and published under: Baumann A, Buchwald D, Annecke T, Hellmich M, Zahn PK, Hohn A. RECCAS - REmoval of Cytokines during Cardiac Surgery: study protocol for a randomised controlled trial. Trials. 2016;17: 137. Graphical abstract

Haemoadsorption has been suggested as treatment adjunct for sepsis and septic shock, cardiac surgery, acute respiratory distress syndrome, and coronavirus disease 2019 (COVID-19). Randomised clinical trials did not provide conclusive evidence for benefits and even suggest risks in COVID-19 patients. Retrospective observational cohort study based on hospital remuneration data from all COVID-19 patients treated in intensive care units in Germany between 01/01/2020 and 12/31/2021. Regression modelling was performed for 1:1 propensity score matching of 2058 patients. Two-sided probability values for group comparisons and regression models with spline functions controlling for non-linear relationships and medically relevant interaction variables were calculated. In-hospital mortality of patients supported with haemoadsorption was significantly higher compared to matched control patients (74.6% vs. 70.3%, p  = 0.0299). Haemoadsorption was associated with coagulopathy (68.0% vs. 54.9%, p  < 0.0001), cardiac arrhythmia (49.2% vs. 44.2%, p  = 0.0272), and cardiopulmonary resuscitation (CPR, 19.3% vs. 13.1%, p  = 0.0002). Further, haemoadsorption increased the chance of death for COVID-19 patients without septic shock (odds ratio, OR [within a 95% confidence interval, CI]; 1.40 [1.05–1.86]) and did not improve survival of septic shock patients (1.19 [0.85–1.67]). Independent variables with a significant impact on mortality included the use of extracorporeal membrane oxygenation (ECMO, 2.15 [1.68–2.76]) and CPR (1.60 [1.03–2.45]). The timing of the haemoadsorption therapy had no effect on patients´ outcomes. Due to inconclusive evidence for benefit and potential harm, haemoadsorption therapy should be limited to thoroughly designed clinical trials before introduced into clinical routine in the context of COVID-19.

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.

OBJECTIVES Sepsis caused by infective endocarditis (IE), due to Staphylococcus aureus, is associated with significant morbidity and mortality. Blood purification using haemoadsorption (HA) may attenuate the inflammatory response. We investigated the effect of intraoperative HA on postoperative outcomes in S. aureus IE. METHODS Patients with confirmed S. aureus IE undergoing cardiac surgery were included in a dual-centre study between January 2015 and March 2022. Patients treated with intraoperative HA (HA group) were compared to patients not treated with HA (control group). The primary outcome was vasoactive-inotropic score within the first 72 h postoperatively and secondary outcomes were sepsis-related mortality (SEPSIS-3 definition) and overall mortality at 30 and 90 days. RESULTS No differences in baseline characteristics were observed between groups (haemoadsorption group, n = 75, control group, n = 55). Significantly decreased vasoactive-inotropic score was observed in the haemoadsorption group at all time points [6 h: 6.0 (0–17) vs 17 (3–47), P = 0.0014; 12 h: 2 (0–8.3) vs 5.9 (0–37), P = 0.0138; 24 h: 0 (0–5) vs 4.9 (0–23), P = 0.0064; 48 h: 0 (0–2.1) vs 0.1 (0–13), P = 0.0192; 72 h: 0 (0) vs 0 (0–5), P = 0.0014]. Importantly, sepsis-related mortality (8.0% vs 22.8%, P = 0.02) and 30-day (17.3% vs 32.7%, P = 0.03) and 90-day overall mortality (21.3% vs 40%, P = 0.03) were also significantly lower with haemoadsorption. CONCLUSIONS Intraoperative HA during cardiac surgery for S. aureus IE was associated with significantly lower postoperative vasopressor and inotropic requirements and resulted in lower sepsis-related and overall 30- and 90-day mortality. In this high-risk population, improved postoperative haemodynamic stabilization by intraoperative HA appears to improve survival and should be further tested in future randomized trials. Postoperative sepsis followed by organ failure is an important cause of morbidity and mortality in patients undergoing cardiac surgery for infective endocarditis (IE) [1]. Staphylococcus aureus (S. aureus) is the leading cause of IE, and the significantly increased mortality rate has remained high despite increasingly effective diagnostic and therapeutic procedures [2, 3].

Background Ex-vivo normothermic perfusion strategies are a promising new instrument in organ transplantation. The perfusion conditions are designed to be protective however the artificial environment can induce a local inflammatory response. The aim of this study was to determine the effect of incorporating a Cytosorb adsorber into an isolated kidney perfusion system. Methods Porcine kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex vivo reperfusion circuit. Pairs of kidneys were randomised to either control (n = 5) or reperfusion with a Cytosorb adsorber (n = 5) integrated into the circuit. Tissue, blood and urine samples were taken for the measurement of inflammation and renal function. Results Baseline levels of cytokines (IL-6, TNFα, IL-8, IL-10, IL-1β, IL-1α) were similar between groups. Levels of IL-6 and IL-8 in the perfusate significantly increased during reperfusion in the control group but not in the Cytosorb group (P = 0.023, 0.049). Levels of the other cytokines were numerically lower in the Cytosorb group; however, this did not reach statistical significance. The mean renal blood flow (RBF) was significantly higher in the Cytosorb group (162 ± 53 vs. 120 ± 35 mL/min/100 g; P = 0.022). Perfusate levels of prostaglandin E2 were significantly lower in the Cytosorb group (642 ± 762 vs. 3258 ± 980 pg/mL; P = 0.0001). Levels of prostacyclin were significantly lower in the Cytosorb group at 1, 3 and 6 h of reperfusion (P = 0.008, 0.003, 0.0002). Levels of thromboxane were also significantly lower in the Cytosorb group throughout reperfusion (P = 0.005). Haemoadsorption had no effect on creatinine clearance (P = 0.109). Conclusion Haemoadsorption can reduce the inflammatory response and improve renal blood flow during perfusion. Nonetheless, in this model haemoadsorption had no influence on renal function and this may relate to the broad-spectrum action of the Cytosorb adsorber that also removes potentially important anti-inflammatory mediators.

Abstract Aim To evaluate the ability of the DrugSorb™-AntiThrombotic Removal (ATR) haemoadsorption device utilizing porous polymer bead sorbent technology to remove three commonly used antithrombotic drugs from whole blood. Methods and results We evaluated the removal of apixaban, rivaroxaban, and ticagrelor by the DrugSorb-ATR haemoadsorption device in a benchtop clinical scale model using bovine whole blood. Blood spiked at clinically relevant concentrations of an antithrombotic agent was continuously circulated through a 300-mL DrugSorb-ATR haemoadsorption device at a flow rate of 300 mL/min. Drug concentration was monitored over 6 h to evaluate drug removal. Results were compared with a control circuit without the haemoadsorption device. Removal rates at 30, 60, 120, and 360 minutes were: apixaban: 81.5%, 96.3%, 99.3% >99.8%; rivaroxaban: 80.7%, 95.1%, 98.9%, >99.5%; ticagrelor: 62.5%; 75%, 86.6%, >95% (all P <0.0001 vs. control). Blood pH and haematological parameters were not significantly affected by the DrugSorb-ATR haemoadsorption device when compared with the control circuit. Conclusion DrugSorb-ATR efficiently removes apixaban, rivaroxaban, and ticagrelor in a clinical-scale benchtop recirculation circuit with the bulk of removal occurring in the first 60 minutes. The clinical implications of these findings are currently investigated in patients undergoing on-pump cardiothoracic surgery in two US pivotal trials (ClinicalTrials.gov Identifiers: NCT04976530 and NCT05093504).

ABSTRACT Background Clearance of circulating myoglobin is crucial to prevent further damage in patients with rhabdomyolysis (RM) and acute kidney injury (AKI). The objective of the present study was to evaluate the efficacy and safety of haemoadsorption (HA) combined with continuous renal replacement therapy (CRRT) in critically ill patients with RM and AKI. Methods Patients with RM and AKI who received CRRT + HA or CRRT with concomitant creatine kinase (CK) >10 000 IU/l in our intensive care unit (ICU) between May 2021 and December 2023 were retrospectively included. The primary outcome was 90-day mortality; secondary outcomes were kidney function recovery and CK decline rate. Adverse events were also evaluated, including hypotension, circuit clotting, albumin leakage and blood loss. Propensity score matching and Cox retrospective analysis were performed. Results A total of 111 RM patients with AKI were ultimately included. The ICU and in-hospital mortality were significantly lower in the CRRT + HA group compared with the CRRT group (ICU mortality: 18% versus 42%, P = .025; in-hospital mortality: 21% versus 42%, P = .048). However, the CRRT + HA group only showed a non-significant reduction in 90-day mortality compared with the CRRT group (47% versus 68%, P = .063). After treatment for 90 days, the number of patients with kidney function recovery was not significantly different between the CRRT + HA and CRRT groups (95% versus 84%, P = .639). Moreover, the incidence of hypotension and circuit clotting events did not increase during CRRT + HA treatment. In addition, the CRRT + HA group also appeared to have a higher rate of CK reduction and reduction of CK than the CRRT group at 24 and 48 hours after the initiation of CRRT. A multivariate Cox regression model demonstrated that CRRT + HA {hazard ratio [HR] 0.477 [95% confidence interval (CI) 0.234–0.972], P = .042}, mean arterial blood pressure [per 1 mmHg; HR 0.967 (95% CI 0.943–0.992), P = .009] and CRRT treatment duration [per 1 h; HR 0.995 (95% CI 0.992–0.998), P = .002] played a favourably important role in the survival prognosis of RM and AKI patients. In contrast, serum phosphate before RRT [per 1 mmol/l; HR 1.531 (95% CI 1.113–2.106), P = .009] and McMahon score [per 1 score; HR 1.15 (95% CI 1.006–1.313), P = .04] were independent risk factors for 90-day mortality. Conclusions CRRT combined with HA therapy reduced ICU and in-hospital mortality in patients with RM and AKI and also had a cleansing effect on creatine kinase without significant adverse events.

Protein-bound uraemic toxins (PBUTs), such as indoxyl sulphate (IS) and p-cresyl sulphate (PCS), are poorly cleared by conventional haemodialysis (HD) or haemodiafiltration (HDF). Haemoadsorption combined with HD (HAHD) using the novel pHA130 cartridge may increase PBUT removal, and this trial aimed to compare its efficacy and safety with HDF in patients with end-stage renal disease (ESRD). In this single-centre, open-label trial, 30 maintenance HD patients were randomized (1:1:1) to HDF once every two weeks (HDF-q2w), HAHD once every two weeks (HAHD-q2w), or HAHD once weekly (HAHD-q1w) for 8 weeks, with the primary endpoint being the single-session reduction ratio (RR) of IS. The combined HAHD group (n = 20) demonstrated a significantly greater IS reduction than the HDF-q2w group (n = 10) (46.9% vs. 31.8%; p = 0.044) and superior PCS clearance (44.6% vs. 31.4%; p = 0.003). Both HAHD regimens significantly reduced predialysis IS levels at Week 8. Compared with HDF, weekly HAHD provided greater relief from pruritus and improved sleep quality, with comparable adverse events among groups. In conclusion, HAHD with the pHA130 cartridge is more effective than HDF for enhancing single-session PBUT removal and alleviating uraemic symptoms in patients with ESRD, with weekly application showing optimal symptomatic benefits.

Infective endocarditis surgical patients suffer from high rates of severe complications such as systemic inflammatory response, septic shock, and multi-organ failure leading to high mortality. Systemic inflammatory response based on cytokines as messengers plays an important role in these patients. The concept of intraoperative haemoadsorption has been proposed to remove such elevated cytokines in patients undergoing cardiac surgery for infective endocarditis. Haemoadsorption offers the possibility to stabilise haemodynamics, reduce sepsis-related mortality, and protect organ function. However, until now, there has been no general opinion and consensus regarding the clinical effectiveness of adjunctive intraoperative haemoadsorption in infective endocarditis. Therefore, we reviewed the current literature evaluating haemoadsorption in infective endocarditis patients undergoing cardiac surgery. The review was registered at PROSPERO (CRD42023457632).