This study aims to investigate the effects of continuous renal replacement therapy (CRRT) combined with ulinastatin on cytokine levels and prognosis in patients with sepsis. The control and study groups (40 cases each) were established. The control group received CRRT alone, while the study group received CRRT plus ulinastatin treatment, with both groups being treated for 7 days. We compared the following parameters before and after treatment between the two groups: Sequential Organ Failure Assessment (SOFA) scores, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, renal function indicators [cystatin C (CysC), blood urea nitrogen (BUN), and serum creatinine (SCr)], inflammatory factors [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and procalcitonin (PCT)], and immune function parameters (CD4+, CD8+, CD4+/CD8+ ratio). Additionally, we recorded adverse reactions and 28-day mortality rates in both groups. After 7 days of treatment, the study group showed significantly lower SOFA scores, APACHE II scores, serum levels of CysC, BUN, Scr, TNF-α, CRP, PCT, and peripheral blood CD8+ compared to the control group, while demonstrating higher peripheral blood CD4+ and CD4+/CD8+ ratio. During the treatment period, there was no significant difference in the incidence of adverse reactions between the two groups. However, the 28-day mortality rate was significantly lower in the study group compared to the control group. For patients with sepsis, the combination of CRRT and ulinastatin therapy can significantly improve disease severity, inflammatory factors, renal function, and immune function, while reducing mortality rate.

While a dysregulated immune response is at the center of the sepsis definition, standard care is still solely focussed on prompt administration of antimicrobial therapy, source control, resuscitation and organ supportive therapies. Extracorporeal blood purification therapies, such as haemoadsorption, have been proposed as a possible adjunctive therapy to standard care in sepsis. These adsorption devices aim to rebalance the dysregulated immune response by removal of excessive amounts of circulating inflammatory mediators, including cytokines and endotoxins. Thus far, the effects of haemoadsorption on clinical outcomes have been insufficiently studied and although its routine use is not justified based on the current evidence, multiple centers use these devices in patients with severe septic shock. This narrative review describes the most well-studied adsorption devices as well as a novel selective adsorption device called the 'IL-6-Sieve', including in vitro data showing its capturing potential. Finally, it addresses important considerations for future trials on haemoadsorption in septic patients.

Background/Objectives: Sepsis, a life-threatening condition caused by a dysregulated immune response to infection, is associated with high mortality. Endotoxin and cytokine overload play a crucial role in sepsis-induced organ dysfunction. The Oxiris® membrane, traditionally used as a hemofilter for renal replacement therapy, has demonstrated the capacity to adsorb endotoxins and cytokines. This study investigates the clinical effect during hemoperfusion with the Oxiris® membrane in patients with septic shock and preserved renal function. Methods: We present three adult patients with septic shock who were admitted to the intensive care unit with high vasopressor requirements and elevated inflammatory markers. As they were refractory to standard therapy and renal function was preserved, a 12-hour hemoperfusion session with an Oxiris® membrane was initiated. Hemodynamic parameters, inflammatory biomarkers, and endotoxin concentrations were evaluated before, during, and after hemoperfusion treatment. Results: All patients demonstrated hemodynamic stabilization, with norepinephrine support reduced by 10.3% to 70.0%. Key inflammatory markers decreased significantly, including interleukin-6 (-41.6% to -94.0%), procalcitonin (-29.3% to -49.5%), and C-reactive protein (4.7% to -37.2%). Endotoxin concentrations decreased by 62.0% and 13.6% in two of the three patients. No adverse effects related to hemoperfusion were observed. Conclusions: Hemoperfusion with the Oxiris® membrane effectively reduced vasopressor support, inflammatory markers, and endotoxin concentrations in patients with refractory septic shock. This approach may offer a novel strategy for early immune modulation in sepsis before renal dysfunction occurs. Further studies with larger cohorts are required to validate these findings and determine optimal treatment protocols.

Polymethyl methacrylate (PMMA) membranes are increasingly recognized for their effectiveness in treating acute kidney injury (AKI) due to their strong adsorption capabilities, particularly for inflammatory mediators like β2-microglobulin and IL-6. These membranes ensure mechanical stability and chemical inertness, minimizing adverse reactions during blood filtration.

In acute conditions such as sepsis and acute respiratory distress syndrome (ARDS), PMMA membranes show promising findings. In sepsis, they may help reduce multiorgan failure by modulating immune responses, although further research is needed to confirm their routine use. For ARDS, PMMA membranes could mitigate "cytokine storms" by adsorbing key cytokines, improving oxygenation and hemodynamic stability, which may reduce ICU stays and reliance on mechanical ventilation. Monitoring biomarkers like IL-6, TNF-α is critical for tracking efficacy and tailoring therapy to individual needs. In chronic conditions, such as hemodialysis for chronic kidney disease, PMMA membranes help lower oxidative stress and β2-microglobulin levels, reducing complications such as amyloidosis. By decreasing oxidative damage, they provide long-term protective benefits for dialysis patients.

While these advantages are notable, large-scale studies are needed to establish PMMA's efficacy, refine treatment protocols, and confirm its broader role in acute and chronic disease management. The potential of PMMA membranes highlights their value, but standardized clinical evidence is necessary for widespread adoption.

The application of high cutoff (HCO) membranes for continuous renal replacement therapy remains unclear in septic acute kidney injury (S-AKI) patients.

S-AKI patients who received continuous veno-venous hemodiafiltration (CVVHDF) were randomly assigned to the experimental group (HCO membrane) and the control group (high flux membrane, HF membrane). Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum and waste fluid were measured at 0, 2, 12, and 24 h after CVVHDF initiation and the 28-day mortality.

Eleven patients were randomized to the HCO group, and 9 patients in the HF group, with a mean age of 54.9 ± 3.2 years and 6 patients (30%) being female. After 24 h of treatment with CVVHDF, there were significant reductions in serum IL-6 and TNF-α concentrations in the HCO group (p = 0.001, 0.015) and HF group (p = 0.004, 0.031). The serum IL-6 reduction rate of the HCO group was significantly higher than that of the HF group (79.21% vs. 42.69%, p = 0.025), while serum TNF-α reduction rates were comparable between the 2 groups. There were no significant changes in serum albumin after 24 h using either HCO membrane (28.7 ± 1.7 g/L vs. 32.7 ± 1.6 g/L, p = 0.138) or HF membrane (29.6 ± 1.1 g/L vs. 32.6 ± 1.3 g/L, p = 0.055). The two groups had similar 24-h filter clotting rates and 28-day mortality.

While CVVHDF with the HCO membrane and HF membrane both achieved significant reductions in serum cytokine levels, the HCO membrane was associated with a greater reduction rate in IL-6 but not in TNF-α. No difference was observed in serum albumin, mortality, or filter clotting.

Registry number: ChiCTR2000039725.

We reported the cytokine profile in children <18 years old who received extracorporeal blood purification (EBP) for sepsis, rhabdomyolysis, hyperbilirubinaemia, acute respiratory distress syndrome or cytokine storm, and determined the factors affecting the cytokine removal kinetics. Plasma levels of 38 types of cytokine/chemokine were measured at pre-EBP, 12 and 24 h after initiating EBP. Altogether there were 11 eligible episodes admitted between April 2021 and December 2023. 72.7% were male with a median (25th, 75th percentile) age of 8.7 (5.4, 15.7) years old. The overall mortality rate was 45.5% but there was no EBP-associated mortality. EBP modalities included Cytosorb® haemoadsorption (63.6%) and Oxiris® haemodiafiltration (36.4%). Thirty-seven (97.4%) cytokines exhibited a concentration reduction following EBP, and 60.5% achieved a ≥50% concentration reduction. The median removal ratio was 35.0 (21.0, 53.7)% at 12 h and 55.0 (42.1, 83.1)% at 24 h. Survivors showed a significantly higher number of cytokines with ⩾50% removal ratio at 24 h (28 vs 7, p = 0.017) and better removal ratio of anti-inflammatory cytokines at 12 h (67.9% vs 0%, p = 0.030). A higher pre-EBP cytokine concentration and higher blood flow rate were significantly associated with better removal in 16 (42.1%) and 32 (84.2%) cytokines respectively. Our study demonstrated that both devices can safely and effectively reduce the cytokine and chemokine levels in critically ill children with various conditions.

Malaria, caused by Plasmodium falciparum (PF), can lead to severe liver dysfunction and hyperbilirubinemia, worsening the prognosis. A 53-year-old male patient with malaria-related liver dysfunction and severe hyperbilirubinemia was treated with extracorporeal hemoadsorption (EHA) with the CytoSorb® filter (CytoSorbents, Monmouth Junction, NJ), marking a turning point in his treatment. This filter, by removing inflammatory mediators and bilirubin, significantly reduced bilirubin levels and improved the patient's clinical condition. This intervention facilitated a bridging therapy, improving symptoms and preventing organ damage during antimalarial treatment. CytoSorb® in EHA shows promise in treating malaria-induced liver dysfunction, suggesting the need for further research on its broader clinical application.

Sepsis is the result of a dysregulated immune response to infection and is associated with acute organ dysfunction. The syndrome's complexity is contingent upon the underlying pathology and individual patient characteristics, including their immune response. The involvement of multiple organs and physiological functions adds complexity, with "organ cross-talk" emerging as a pivotal pathophysiological and clinical aspect. This narrative review to evaluate the rationale and available clinical evidence supporting the use of extracorporeal blood purification therapies as adjunctive therapy in patients with sepsis and septic shock.

A search of the PubMed, Embase, Web of Science and Scopus databases for relevant literature from August 2002 to May 2024 has been conducted. The search was performed using the terms: 1) "blood purification" or "hemadsorption" or "plasma exchange" AND 2) "sepsis" or "septic shock". Therefore the authors have focused our discussion on several key areas such as conducting well-designed trials, developing more personalized protocols, ensuring optimal management and monitoring.

Given the heterogeneity of patients with sepsis, conducting traditional randomized clinical trials in this domain can be a daunting task. However, statistical techniques such as Bayesian methods, propensity score analysis, and emulated clinical trials using clinical databases hold promise for enhancing comparability between the study groups. Indeed, to comprehend the clinical efficacy of extracorporeal blood purification techniques in patients with sepsis, it is imperative to assemble homogeneous groups of patients receiving uniform treatments. Clinical strategies should be individualized, signaling the end of the "one size fits all" approach in sepsis therapy and the need for personalized treatments.

Background/Objectives: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a major challenge in ICUs. This study evaluated whether combining haemoadsorption therapy with continuous renal replacement therapy (CRRT) reduces ICU and short-term mortality in patients with severe septic shock and acute kidney injury (AKI) requiring CRRT. Methods: A single-centre retrospective cohort study was conducted at Rambam Health Care Campus, Haifa, Israel, from January 2018 to February 2024. Data were collected from ICU patients with severe septic shock and AKI requiring CRRT. Patients were divided into two groups: those receiving haemoadsorption therapy with CRRT and those receiving CRRT alone. Primary and secondary endpoints included ICU, 30 and 60-day mortality, vasopressor dependency index (VDI), and lactate levels. Results: Out of 545 patients with septic shock, 133 developed AKI requiring CRRT, and 76 met the inclusion criteria. The haemoadsorption group (n = 47) showed significant reductions in blood lactate levels and VDI after 24 h compared to the CRRT alone group (n = 29). ICU mortality was significantly lower in the haemoadsorption group (34.0% vs. 65.5%, p = 0.008), as was 30 and 60-day mortality (34.0% vs. 62.1%, p = 0.02, and 48.9% vs. 75.9%, p = 0.002). Multivariate analysis confirmed haemoadsorption therapy as independently associated with lower ICU and 30-day but not 60-day mortality. Conclusions: Haemoadsorption therapy combined with CRRT in patients with severe septic shock and AKI requiring CRRT is associated with improved lactate clearance, reduced vasopressor requirements, and lower ICU and 30-day mortality. Further high-quality randomized controlled trials are needed to confirm these findings.

Cardiac surgery patients are potentially exposed to an acute inflammatory host response with a huge release of both pro- and anti-inflammatory cytokines both through intrinsic (e.g., tissue damage, endothelial injury) and extrinsic (e.g., anesthesia, extracorporeal circuits) mechanisms. Current standard of care therapy includes several invasive supportive treatments such as mechanical ventilation, continuous renal replacement therapy, ECMO, and/or cardiopulmonary bypass which may be responsible for an important inflammatory response. The inflammatory cytokine levels and hemodynamic status following these artificial treatments along with the current standard therapy are not always well controlled and may lead to worsened acute clinical conditions with prolonged in-hospital length of stay and increased mortality. In these settings, the administration of hemadsorption therapy with CytoSorb® has been supported by the successful results in several clinical studies as it has shown improvement of both the inflammatory profile and the hemodynamic vascular status of the patients. Therefore, in this narrative review, we summarized and discussed the current scientific literature on the role of CytoSorb® treatment in case of cardiac surgery. According to the current evidences, the raised inflammatory levels and both inotropic and vasopressor requests in cardiac surgery patients need more tailored therapies and, in this contest, the hemadsorption with CytoSorb® could play a pivotal role, especially on heart transplant patients. Furthermore, CytoSorb is currently the only hemadsorption sorbent authorized and efficiently applied for removing anticoagulant agents such as ticagrelor or rivaroxaban in patients undergoing cardiac surgery, to reduce perioperative bleeding complications and should be considered in high-risk patients.

Background: Renal replacement therapy with an oXiris hemofilter may be helpful for patients with acute kidney injury in conjunction with sepsis and septic shock. The aim of this study was to assess the impact of an oXiris membrane on septic shock patients. Methods: All renal replacement therapies with oXiris (Baxter, Deerfield, IL, USA) performed between January 2018 and August 2021 were retrospectively analyzed. CRRT was initiated in continuous venovenous hemodiafiltration (CVVHDF) mode using Prismaflex System (Baxter). Demographic data, starting point of infection, source control, etiology, and course of treatment were analyzed. Results: A total of 32 patients were included in the study. Most patients treated with oXiris had acute kidney injury (AKI) and required CRRT. One patient had KDIGO 1 AKI (3.1%), three patients (9.4%) had KDIGO 2 AKI, and 28 patients (87.5%) had KDIGO 3 AKI. A statistically significant decrease in vasopressin dosage was required to achieve adequate MAP after 24 and 72 h, and a statistically significant decrease in norepinephrine dosage after 72 h was observed, with no SOFA score change on days 2 and 3. Procalcitonin and lactate levels did not change after 24 and 72 h. No beneficial effect on mortality was observed. Conclusions: Treatment with an oXiris membrane can positively impact vasopressors' requirement but not influence SOFA score, procalcitonin or lactate levels, or mortality in septic shock patients.

Hemoperfusion (HP) is an extracorporeal blood purification modality utilized to remove small- to medium-sized molecules, such as toxins and cytokines, that are difficult to remove by conventional hemodialysis. In clinical practice, HP has been successfully used as a salvage therapy for drug overdose and occasionally in patients with liver failure and sepsis.

To summarize the clinical outcomes of a series of patients with severe coronavirus disease 2019 (COVID-19) who received HP.

Here, we summarize the clinical outcomes of a series of 18 patients with severe COVID-19 who received HP in our institution during the COVID-19 pandemic. A review of the literature was also performed.

HP was well-tolerated, and after an average of three sessions, respiratory and cardiovascular parameters as well as blood inflammatory markers improved in most patients. Ten patients were discharged alive. Our literature search identified a total of 20 studies (873 patients) in which HP was used for COVID-19. Nine studies reported improvements in respiratory parameters, and 13 studies (438 patients in total) reported better survival rates in patients undergoing HP.

HP was well-tolerated in patients with severe COVID-19, and most studies reported improved clinical parameters, including better survival rates, when HP was used in patients with severe COVID-19. Further research, especially prospective studies, is needed to evaluate the utility of HP as an early and supportive therapy for critically ill patients due to infectious diseases, such as those with COVID-19 or severe sepsis.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant problem following cardiopulmonary bypass (CPB). Various strategies are proposed to attenuate CSA-AKI, including extracorporeal blood purification (EBP), but little is known about the effect of EBP through an acrylonitrile-sodium methallylsulfonate/polyethyleneimine membrane during CPB.

To determine whether the use of an EBP device in a nonemergent cardiac surgery population reduces CSA-AKI after CPB.

This double-blind, randomized clinical trial was conducted in 2 tertiary hospitals in Spain. Patients 18 years or older undergoing nonemergent cardiac surgery who were at high risk for CSA-AKI were enrolled from June 15, 2016, through November 5, 2021, with follow-up data through February 5, 2022. Of 1156 patients assessed, 343 patients were randomized (1:1) to either receive EBP or standard care.

Nonselective EBP device connected to the CPB circuit.

The primary outcome was the rate of CSA-AKI in the 7 days after randomization.

Among 343 patients randomized (169 to receive EBP and 174 to receive usual care), the mean (SD) age was 69 (9) years and 119 were females. The rate of CSA-AKI was 28.4% (95% CI, 21.7%-35.8%) in the EBP group vs 39.7% (95% CI, 32.3%-47.3%) in the standard care group (P = .03), with an adjusted difference of 10.4% (95% CI, 2.3%-18.5%) using a log-binomial model (P = .01). No significant differences (P > .05) were observed in most of the predefined clinical secondary end points or post hoc exploratory end points. In a sensitivity analysis, EBP was found to be more effective in terms of CSA-AKI reduction in patients with chronic kidney disease, diabetes, hypertension, low left ventricular ejection fraction (<40%), and lower body mass index (<30). No differences were observed between the groups in adverse events tracking.

The use of a nonselective EBP device connected to the CPB circuit in a nonemergent population of patients undergoing cardiac surgery was associated with a significant reduction of CSA-AKI in the first 7 days after surgery.

ClinicalTrials.gov Identifier: NCT02518087.

Cytokine-adsorption therapy has garnered attention as a potential treatment for conditions such as sepsis, although supporting evidence remains limited. Consequently, its utilization is expected to vary significantly across regions. To date, no ecological studies have investigated this regional heterogeneity.

This study aimed to examine temporal trends in the use of continuous renal replacement therapy (CRRT) with cytokine-adsorbing hemofilters and polymyxin-B immobilized fiber-direct hemoperfusion (PMX-DHP), as well as the spatial distribution of both across Japan's 47 prefectures.

This ecological study analyzed National Database (NDB) open data. A longitudinal analysis from 2016 to 2022 assessed temporal trends in the use of adsorption membranes. A cross-sectional analysis of the 2022 data utilized Moran's I statistic to evaluate the spatial autocorrelation of adsorption therapy. To examine the relationship between the two types of adsorption therapy, we calculated the Pearson correlation coefficient and conducted a multivariate analysis.

The longitudinal analysis revealed no significant change in the proportion of cytokine-adsorbing hemofilter use, while PMX-DHP use showed a decreasing trend over the seven-year period. Cross-sectional analysis indicated spatial autocorrelation for both PMX-DHP (Moran's I: 0.34, P < 0.001) and cytokine-adsorption filter use (Moran's I: 0.24, P < 0.001). Univariate analysis (R = -0.29, P = 0.0453) and multivariate analysis (estimated coefficient: 1.27, 95% CI: 0.06-2.49, P = 0.045) demonstrated that higher usage rates of cytokine-adsorbing blood filters were associated with higher PMX-DHP usage rates.

This study identified a declining trend in PMX-DHP use and an association between PMX-DHP and cytokine-adsorbing hemofilter utilization. These findings suggest that physicians' preferences and perceptions regarding cytokine-adsorption therapy may influence its use. Further research with individual patient data is warranted to confirm these findings.

We describe the case of a 72-year-old male with a history of systemic mastocytosis scheduled for on-pump aortic valve replacement for severe aortic insufficiency. Anesthesia and peri-operative management included avoidance of histamine-releasing drugs, methylprednisolone and clemastin prophylaxis. Furthermore, a CytoSorb ® cartridge has been added to the bypass circuit and hemoadsorption was performed throughout the entire cardiopulmonary bypass (CPB) duration. CytoSorb ® is a hemoadsorption device designed to remove various cytokines and drugs from the blood. The use of CytoSorb ® during CPB in our case was not associated with adverse events, and the patient did not present any allergic or anaphylactic reaction.

Objective: The objective of this study is to assess and compare the efficacy of oXiris with conventional continuous renal replacement therapy (CRRT) in managing severe abdominal infections. Methods: A retrospective analysis encompassing cases from 2017 to 2023 was conducted at the Department of Critical Care Medicine within the First Affiliated Hospital of Fujian Medical University. Parameters including heart rate (HR), mean arterial pressure (MAP), oxygenation index, lactate (Lac), platelet count, neutrophil ratio, procalcitonin, C-reactive protein (CRP), interleukin 6 (IL-6), norepinephrine dosage, Acute Physiology and Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) were recorded prior to treatment initiation, at 24 h, and 72 h after treatment for both the oXiris and conventional CRRT groups. In addition, the duration of respiratory support, CRRT treatment, length of stay in the intensive care unit (ICU), total hospitalization period, and mortality rates at 14 and 28 days for both groups were recorded. Results: 1) Within the conventional CRRT group, notable enhancement was observed solely in Lac levels at 24 h after treatment compared with pretreatment levels. In addition, at 72 h after treatment, improvements were evident in HR, Lac, CRP, and IL-6 levels. 2) Conversely, the oXiris group exhibited improvements in HR, MAP, Lac, oxygenation index, neutrophil ratio, and IL-6 at 24 h after treatment when compared with baseline values. In addition, reductions were observed in APACHE II and SOFA scores. At 72 h after treatment, all parameters demonstrated enhancement except for platelet count. 3) Analysis of the changes in the indexes (Δ) between the two groups at 24 h after treatment revealed variances in HR, MAP, Lac, norepinephrine dosage, CRP levels, IL-6 levels, APACHE II scores, and SOFA scores. 4) The Δ indexes at 72 h after treatment indicated more significant improvements following oXiris treatment for both groups, except for procalcitonin. 5) The 14-day mortality rate (24.4%) exhibited a significant reduction in the oXiris group when compared with the conventional group (43.6%). However, no significant difference was observed in the 28-day mortality rate between the two groups. 6) Subsequent to multifactorial logistic regression analysis, the results indicated that oXiris treatment correlated with a noteworthy decrease in the 14-day and 28-day mortality rates associated with severe abdominal infections, by 71.3% and 67.6%, respectively. Conclusion: oXiris demonstrates clear advantages over conventional CRRT in the management of severe abdominal infections. Notably, it reduces the fatality rates, thereby establishing itself as a promising and potent therapeutic option.

To evaluate the efficacy of the novel oXiris® membrane in critically ill adult patients.

We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to 01/06/2023 for relevant randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSI). The primary outcome was overall mortality. Random effect meta-analyses were conducted in RevMan 5.4.1. Study quality was evaluated using Cochrane's risk of bias tool. (PROSPERO: CRD42023389198).

Ten studies (2 RCTs and 8 NRSIs) with 481 patients were included. None had low risk of bias. Treatment using oXiris® was associated with reduced overall mortality (RR 0.78, 95%CI 0.62-0.98; p = 0.03; 6 NRSI). One RCT reported 28-day mortality, finding no significant difference between groups. Besides, pooled NRSIs results showed significant reductions in SOFA scores, norepinephrine dosage, and several inflammatory biomarkers (C-reactive protein [CRP], lactate, and interleukin-6 [IL-6]) post oXiris® treatment. However, other clinical outcomes (ICU and hospital length of stay, mechanical ventilation duration) were similar between groups.

In critically ill patients, the use of oXiris® membrane was associated with reduced overall mortality, norepinephrine dosage, CRP, IL-6, lactate levels, along with improved organ function. However, the certainty of evidence was very low, necessitating high-quality RCTs to further evaluate its efficacy in this population.

Castleman disease (CD) is a rare lymphoproliferative disorder, with non-specific clinical manifestations, often delayed diagnosis and treatment, which pose a significant challenge in the present times. Patients diagnosed with this disease have poor prognosis due to the limited treatment options. Multicentric CD occurs at multiple lymph node stations and is associated with a proinflammatory response that leads to the development of the so-called 'B symptoms'. IL-6 seems to be a key cytokine involved in various manifestations such as lymphadenopathies, hepatosplenomegaly, and polyclonal hypergammaglobulinemia. Its levels correlate with the activity of the disease. Other consequences of MCD include increased fibrinogen levels leading to deep vein thrombosis and thromboembolic disorders, high hepcidin levels causing anaemia, elevated VEGF levels promoting angiogenesis and vascular permeability, which, along with hypoalbuminemia, induce oedema, ascites, pleural and pericardial effusions, and in severe cases, generalized anasarca. In extreme cases multiple organ failure can occur, often resulting in death. We propose the use of continuous renal replacement therapy (CRRT) in managing severe multicentric CD. Our arguments are based on the principles that CRRT is able to remove IL-6 from circulation thus attenuating the cytokine storm, can influence hepcidin levels, and reduction in oedema, and is often used in multiple organ failure to regain homeostasis control. Therefore, it could be used as a therapy or bridge therapy in severe cases. To sustain our hypothesis with evidence, we have gathered several studies from the literature confirming the successful removal of cytokines, especially IL-6 from circulation, which can be used as a starting point.

The clinical effectiveness of Oxiris®, particularly in reducing cytokines, remains uncertain due to the limited data provided. This study explored and analyzed the application value of Oxiris® endotoxin adsorption technology in a large animal model. Pigs received an intravenous LPS infusion. Six animals were treated 2 h after the infusion with an Oxiris® hemadsorption using a pumpless extracorporeal technique for 6 h. Five animals served as controls. Cardiocirculatory parameters, hyperspectral analysis, and a panel of cytokines were measured. The lipopolysaccharide infusion induced sepsis-like inflammation with tachycardia, elevated pulmonary pressure, elevated lactate level, as well as elevated pro-inflammatory cytokines like interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-12 and tumor necrosis factor alpha (TNF-α). In addition, increases of anti-inflammatory cytokines like IL-1ra and IL-10 were found. After 3 and 6 h in both groups, pro-inflammatory cytokines were significantly reduced. No differences between the intervention and the control group could be detected after 3 and 6 h for IL-1β, IL-2, IL-6, IL-8, IL-12 and TNF-α, suggesting no effect of the Oxiris® filter on the elimination of elevated cytokines with a pumpless extracorporeal hemadsorption technique. The presented large animal model may be a promising option for studying the effects of hemadsorption techniques.

Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48-1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17-1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18-0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

Within patients with sepsis, there exists significant heterogeneity, and while all patients should receive conventional therapy, there are subgroups of patients who may benefit from specific therapies, often referred to as rescue therapies. Therefore, the identification of these specific patient subgroups is crucial and lays the groundwork for the application of precision medicine based on the development of targeted interventions. Over the years, efforts have been made to categorize sepsis into different subtypes based on clinical characteristics, biomarkers, or underlying mechanisms. For example, sepsis can be stratified into different phenotypes based on the predominant dysregulated host response. These phenotypes can range from hyperinflammatory states to immunosuppressive states and even mixed phenotypes. Each phenotype may require different therapeutic approaches to improve patient outcomes. Rescue strategies for septic shock may encompass various interventions, such as immunomodulatory therapies, extracorporeal support (e.g., ECMO), or therapies targeted at specific molecular or cellular pathways involved in the pathophysiology of sepsis. In recent years, there has been growing interest in precision medicine approaches to sepsis and phenotype identification. Precision medicine aims to tailor treatments to each individual patient based on their unique characteristics and disease mechanisms.

The main objective of this study was to evaluate the impact of hemoadsorption on the elimination of inflammatory mediators.

A prospective, bicenter, observational cohort study was conducted between March 2020 and February 2022 to explore the immunomodulatory response, demographic and clinical characteristics of individuals with COVID-19 admitted to the ICU with severe acute respiratory failure and in need of CRRT with Oxiris® with or without AKI.

Sixty-four patients were analyzed. Statistically significant differences were observed between exposed and unexposed groups, in relation to the reduction in D-dimer levels -15,614 (24,848.9) versus -4,136.5 (9,913.47) (p 0.031, d: 1.59, 95% CI: -21,830, -1,126). An increase in PCT was observed 0.47 (2.08) versus -0.75 (2.3) (p 0.044 95% CI: 0.03, 2.44). No differences were found in a decrease in CRP -4.21 (7.29) versus -1.6 (9.02) (p 0.22) nor in the rest of inflammatory parameters fibrinogen, IL-6, ferritin, lymphocytes, and neutrophils. Subgroup analysis in patients exposed to therapy also showed a significant decrease in D-dimer of 55% from baseline: 6,000 (1,984.5-27,750) pre-therapy versus 2,700 (2,119.5-6,145) (95% CI: -23,000, -2,489) post-therapy with a strong effect size (p 0.001, d: 0.65).

The hemoadsorptive therapy in COVID-19 was associated with a significant decrease in D-dimer parameters without showing decreases in the rest of the clinical, inflammatory parameters and severity scales analyzed.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

The coronavirus disease 2019 (COVID-19) pandemic represented a global public health problem with devastating consequences that have challenged conventional medical treatments. Continuous renal replacement therapy (CRRT), based on a spectrum of modalities and dialysis membranes, can modify cytokine storms, and improve the clearance of inflammatory factors. As severe COVID-19 can lead to acute kidney injury (AKI) requiring RRT, most patients require more than one extracorporeal organ support at this point. This is due to complications that lead to organ dysfunction. The aim of our study was to assess renal recovery and survival while use of the oXiris membrane, as well as a decrease in vasopressors and hemodynamic parameters.

This was a retrospective, observational study. The population included adult patients (aged >18 years) with a real-time PCR COVID-19 positive test, admitted to the intensive care unit (ICU) with AKI KDIGO 3, which required CRRT, in a hospital in northern Mexico. The primary outcomes were renal recovery and survival, and the secondary outcomes were a decrease in the vasopressor requirements and changes in the hemodynamic parameters.

Thirteen patients were included from January 2020 to August 2021, all of whom met the inclusion criteria. oXiris, an AN69-modified membrane, was used for blood purification and cytokine storm control in all the patients. The primary outcome, renal recovery, and survival were observed in 23% of the patients. The secondary outcome was a decrease of 12% in the use of noradrenaline in the first 24 h of CRRT initiation with oXiris, in addition to a decrease in creatinine and C-reactive protein levels in all patients.

The use of the oXiris membrane in patients with severe COVID-19 improved hemodynamic parameters, with 23% of the patients achieving renal recovery. The decrease on the requirement of vasopressors in the overall patients in the first 24 h of CRRT with oXiris was achieved. The mean decrease was of 12%, accompanied by a decrease in inflammatory markers. There is literature on the benefit of CRRT with a modified AN69 membrane in Mexico; however, studies in this regard are scarce, and our research provides valuable information on our experience in this field.

Extracorporeal haemofiltration devices that selectively remove cytokines could represent an adjunctive treatment in inflammatory diseases. One such device is the "IL-6-Sieve", wherein magnetic Anti-IL-6 Beads are introduced into an extracorporeal circuit via a Bead Adapter and then removed along with any surface-bound interleukin (IL)-6 by a Filter deployed in a Magnet, before the blood is returned to the patient. We report here on a series of animal studies, and a first-in-human study, on the safety of the IL-6-Sieve. Evaluations focused on the: (a) safety of Filter and Magnet placed in an extracorporeal circuit in sheep; (b) safety of Anti-IL-6 Beads-directly infused intravenously as worst case scenario of misuse; or injected into an extracorporeal circuit using the Bead Adapter, Filter, and Magnet as intended-in sheep; (c) biodistribution of Anti-IL-6 Beads intravenously infused in mice; and (d) safety of Filter and Magnet placed in an extracorporeal circuit in healthy volunteers. No serious adverse events or significant changes in vital signs or routine laboratory parameters occurred in any of the animals or humans. Although safety of the IL-6-Sieve requires further study, these initial evaluations represent a promising start for the translation of this new blood purification modality into clinical use.

CytoSorb is a hemoadsorptive column used to remove high concentrations of proinflammatory cytokines in septic shock. Data on CytoSorb application in acute-on-chronic liver failure (ACLF) is lacking. This retrospective observational study analyzed 21 ACLF patients admitted to ICUs at the Vienna General Hospital who received CytoSorb adsorber therapy between 2017 and 2023. Median ICU length of stay was 8 days (IQR: 3-13), the ICU survival rate was 23.8% (n = 5). Significant decreases in bilirubin (median peak: 20.7 mg/dL to median post-treatment: 10.8 mg/dL; - 47.8%; p < 0.001), procalcitonin (1.34 to 0.74 pg/mL; - 44.6%; p < 0.001), interleukin-6 (385 to 131 ng/mL; - 66.0%; p = 0.0182)-but also of platelets (72 to 31 G/L; - 56.9%; p = 0.0014) and fibrinogen (230 to 154 mg/dL; - 33.0%; p = 0.0297) were detected. ICU survivors had a trend towards a stronger relative decrease in bilirubin (- 76.1% vs. - 48.2%), procalcitonin (- 90.6% vs. - 23.5%), and IL-6 (- 54.6% vs. - 17.8%) upon CytoSorb treatment. Moreover, no serious CytoSorb-attributed complications were detected. In conclusion, use of CytoSorb adsorber in ACLF patients results in a significant decrease in bilirubin and proinflammatory cytokines, while platelets and fibrinogen were also lowered. Prospective trials are warranted to investigate the impact of CytoSorb on clinical outcomes of ACLF patients with high proinflammatory cytokine levels.

Capnocytophaga canimorsus is a Gram-negative bacterium, commonly found as a commensal germ in the oral cavity of dogs and cats. It is an opportunistic pathogen, but, in specific situations, it can cause very severe diseases, including arthritis, pleuritis, endocarditis, sepsis, and, in extremely rare cases, meningoencephalitis. The predisposing situations include immunosuppression, liver cirrhosis, splenectomy, hemochromatosis, beta thalassemia major (Cooley's anemia), and alcohol abuse. In this report, we describe the case of a 48-year-old male patient, with a medical history of several predisposing conditions, who developed a severe case of meningoencephalitis caused by C. canimorsus, following a dog bite on his hand. The patient was successfully treated for his meningitis, but subsequently he developed a hospital-acquired septic shock from Acinetobacter baumannii, which was treated with targeted antibiotic therapy and sequential extracorporeal blood purification therapies using Oxiris™ and Toraymyxin™ hemofilters.

The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment.

Prospective randomized large-animal peritoneal septic shock experiment.

Laboratory investigation.

Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8).

Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse.

Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia.

In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.

Streptococcal toxic shock syndrome (STTS) is a critical medical emergency marked by high morbidity and mortality, necessitating swift awareness, targeted treatment, and early source control due to its rapid symptom manifestation. This report focuses on a cohort of 13 patients admitted to Vall d'Hebron University Hospital Intensive Care Unit, Barcelona, from November 2022 to March 2023, exhibiting invasive Streptococcus pyogenes infections and meeting institutional sepsis code activation criteria. The primary infections were community-acquired pneumonia (61.5%) and skin/soft tissue infection (30.8%). All patients received prompt antibiotic treatment, with clinical source control through thoracic drainage (30.8%) or surgical means (23.1%). Organ support involved invasive mechanical ventilation, vasopressors, and continuous renal replacement therapy as per guidelines. Of note, 76.9% of patients experienced septic cardiomyopathy, and 53.8% required extracorporeal membrane oxygenation (ECMO). The study identified three distinct phenotypic profiles-hyperinflammatory, low perfusion, and hypogammaglobulinemic-which could guide personalized therapeutic approaches. STTS, with a mean SOFA score of 17 (5.7) and a 53.8% requiring ECMO, underscores the need for precision medicine-based rescue therapies and sepsis phenotype identification. Integrating these strategies with prompt antibiotics and efficient source control offers a potential avenue to mitigate organ failure, enhancing patient survival and recovery in the face of this severe clinical condition.

Sepsis and septic shock are associated with high mortality, with diagnosis and treatment remaining a challenge for clinicians. Their management classically encompasses hemodynamic resuscitation, antibiotic treatment, life support, and focus control; however, there are aspects that have changed. This narrative review highlights current and avant-garde methods of handling patients experiencing septic shock based on the experience of its authors and the best available evidence in a context of uncertainty. Following the first recommendation of the Surviving Sepsis Campaign guidelines, it is recommended that specific sepsis care performance improvement programs are implemented in hospitals, i.e., "Sepsis Code" programs, designed ad hoc, to achieve this goal. Regarding hemodynamics, the importance of perfusion and hemodynamic coherence stand out, which allow for the recognition of different phenotypes, determination of the ideal time for commencing vasopressor treatment, and the appropriate fluid therapy dosage. At present, this is not only important for the initial timing, but also for de-resuscitation, which involves the early weaning of support therapies, directed elimination of fluids, and fluid tolerance concept. Finally, regarding blood purification therapies, those aimed at eliminating endotoxins and cytokines are attractive in the early management of patients in septic shock.

Apheresis is a modern medical approach in which plasma or cellular components are separated from the whole blood. Apheresis can be either diagnostic or therapeutic. Diagnostic apheresis is typically applied in hematology and cancer research. Therapeutic Apheresis (TA) includes a broad spectrum of extracorporeal treatments applied in various medical specialties, including Intensive Care Unit (ICU). Considering the complexity of the pathophysiologic characteristics of various clinical entities and in particular sepsis, apheresis methods are becoming increasingly applicable. Therapeutic Plasma Exchange (TPE) is the most common used method in ICU. It is considered as first line therapy for Thrombotic Thrombocytopenic Purpura (TTP) and Guillain Barre Syndrome, while the current data for sepsis are scarce. Over the last decades, technologic evolution has led to increasing application of new and more selective methods based on adsorptive techniques. In this review we will describe the current data of characteristics of different techniques, safety and clinical impact of apheresis methods used in ICUs.

In septic shock patients, pathogens and excessive endotoxins continuously overstimulate the host's immune system with a cytokine storm that can lead to multi-organ failure and even mortality. Various types of extracorporeal blood purification treatments have recently been introduced to remove excessive endotoxins and cytokines. Herein, we compared the clinical efficacy of two blood purification methods, PMX-HP and AN69-oXiris, and discussed their detailed indications according to disease severity.

From December 2016 to April 2023, patients who underwent emergent surgery due to septic shock secondary to peritonitis and subsequently received blood purification treatment with AN69-oXiris or PMX-HP were enrolled. Propensity score (PS)-matching was conducted to adjust for baseline characteristics between the two groups, and the changes in clinical parameters and outcomes were compared. Clinical outcomes were assessed in subgroups of patients who underwent PMX-HP treatment divided according to SOFA scores into low (0-7), intermediate (8-13), and high (> 13) disease severity groups.

Forty patients received blood purification therapy with either PMX-HP or AN69-oXiris during the study period. After 1:2 PS matching, six patients in the AN69-oXiris group and 12 patients in the PMX-HP group were finally analyzed. Vasoactive-inotropic scores (VISs) decreased in both groups after 48 h of treatment compared to the baseline values, but the change in VISs was more pronounced in the PMX-HP group {-57.6 [interquartile range (IQR) = -166.4 - (-10)] vs. -22.9 [IQR = -64-0], respectively, p = 0.041}. Decreases in cardiovascular SOFA scores were significantly pronounced in the PMX-HP group [-1.5 (IQR = -4 - 0) vs. 0 (IQR = -1 - 1), respectively, p = 0.035]. The 7-day mortality rate was significantly lower than the predicted mortality rate in a subgroup analysis of patients treated with PMX-HP in both the low disease severity group and the intermediate disease severity group.

PMX-HP and AN69-oXiris could be therapeutic options for refractory septic shock patients with intra-abdominal origins, especially after the surgical elimination of the infectious sources. A tailored modality choice that takes into account patient characteristics, such as disease severity and cost burden, could optimize the efficacy of this strategy.

Infective endocarditis (IE) is a rare but severe disease with high morbidity and mortality. Cardiac surgery plays a major role in the contemporary clinical management of IE patients. During cardiac surgery, cardiopulmonary bypass significantly contributes to an increased risk of organ dysfunction and mortality by inducing an acute inflammatory response, vascular endothelial cell injury, impairment of the coagulation cascade, and ischemia-reperfusion injury. During the past decade, the use of extracorporeal hemoadsorption therapy with the CytoSorb® hemoadsorber (CytoSorbents Europe GmbH, Berlin, Germany) has been proposed as an adjuvant therapy to mediate inflammatory responses in IE patients undergoing cardiac surgery with cardiopulmonary bypass. However, there is currently no systematic evaluation of the effect of CytoSorb® hemoadsorption on clinical outcomes such as hemodynamics, organ dysfunction, and mortality in patients with IE. Therefore, in this review, we exclusively discuss contemporary findings concerning the rationale, clinical evidence, and future perspectives for CytoSorb® hemoadsorption therapy in IE patients.

Cytokine storm syndromes (CSS) include different entities such as macrophage activation syndrome, primary and secondary hemophagocytic lymphohistiocytosis (HLH), and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. An effective management strategy is critical in CSS. While biologics have become an essential part of CSS treatment, hematopoietic stem cell transplantation (HSCT) has changed the fate of primary HLH patients. This chapter will focus on the available alternative immunomodulatory therapies in CSS, which include corticosteroids, cyclosporine A, intravenous immunoglobulin, interleukin 18 binding protein, therapeutic plasmapheresis, HSCT, and mesenchymal stromal cell-based therapies.

Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels.

Multiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia.

In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1-42]%, oXiris: 21 [10-51]%, Toraymyxin: 23 [10-36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22).

In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care. Trial registration ClinicalTrials.gov. NCT01948778. Registered August 30, 2013. https://clinicaltrials.gov/study/NCT01948778.

The effectiveness of CytoSorb at removing inflammatory mediators in critically ill patients is controversial.

Electronic databases were searched from inception to May 2023.

Randomized controlled trials reporting the effects of CytoSorb therapy on inflammatory parameters in critically ill patients with hyperinflammatory conditions were included.

Two authors screened articles for eligibility, extracted data, and assessed the risk of bias, conflicts of interest, and certainty of evidence (CoE). The primary outcome was interleukin (IL)-6 at 1 day after initiation of the therapy. Secondary outcomes included various inflammatory markers at 1, 2, 3, and 5 days and mortality. Data were pooled if at least three trials reported the outcome of interest. We conducted meta-analyses of the data using a random-effects model.

Seventeen trials ( n = 855) were included. Fourteen trials were judged to have notable concern about conflicts of interest. Seven trials were performed in medical ICU patients with hyperinflammatory conditions and 10 in complex cardiovascular surgery under cardiopulmonary bypass. Hemoadsorption with CytoSorb was not associated with lower IL-6 at 1 day (mean difference -5.98 [95% CI, -30.44 to 18.48] pg/mL), 2 days, 3 days, or 5 days after initiation of the treatment, as well as the concentration of procalcitionin. The levels of C-reactive protein were not lower with CytoSorb at 1, 2, and 3 days. The use of CytoSorb was associated with higher mortality at latest follow-up (relative risk = 1.22 [95% CI, 1.02-1.45]) and at 30 days. CoE ranged from low to very low.

The use of CytoSorb hemoadsorption in a mixed population of critically ill patients with hyperinflammatory conditions does not exhibit a consistent decrease in IL-6 and other inflammatory parameters within the first 5 days of treatment. The significant uncertainty surrounding these findings highlights the need for further investigations.

Endotoxin, also referred to as lipopolysaccharide (LPS), is a potent stimulator of the inflammatory cascade which may progress to sepsis and septic shock. The term endotoxic septic shock has been used for patients who have a clinical phenotype that is characterized by high endotoxin activity in addition to a high burden of organ failure; especially a pattern of organ failure including hepatic dysfunction, acute kidney injury, and various forms of endothelial dysfunction. Endotoxic septic shock has been a target for drug therapy for decades with no success. A likely barrier to their success was the inability to quantify endotoxin in the bloodstream. The Endotoxin Activity Assay (EAA) is positioned to change this landscape. In addition, medical devices using adsorptive technology in an extra-corporeal circulation has been shown to remove large quantities of endotoxin from the bloodstream. Focusing on the use of EAA to determine high concentrations of endotoxin will allow patients with endotoxic septic shock to be identified quickly and these patients may benefit most from removal of endotoxin using extracorporeal methods.

During the coronavirus disease 2019 (COVID-19) pandemic, acute kidney injury (AKI) was a common sequela of COVID-19 infection and predicted disease severity and mortality. Extracorporeal blood purification techniques involving blood filtration devices are an emerging treatment for AKI in the setting of severe COVID-19 infections. In this review, we discuss potential mechanisms for the development of AKI in COVID-19 patients as well as the various available blood filtration devices and the role they may play in managing the AKI in COVID-19 patients. A total of seven blood filters currently available were compared based on their potential in treating AKI in COVID-19 patients. Blood filtration devices show potential as an emerging treatment modality for COVID-19-induced AKI, but further clinical trials are necessary before their widespread adoption and usage.

Hemoadsorption shows promising signals in organ preservation and post lung transplantation. However, its potential impact on the pharmacokinetics of immunosuppressant drugs (ID) is still unknown.

In this interventional study, CytoSorb® hemoperfusion was tested in healthy sheep (n = 5) against a sham extracorporeal circuit (n = 3). Seven different ID (tacrolimus (TAC), cyclosporin A (CYA), mycophenolate mofetil (MMF), everolimus (EVER), basiliximab (BAS), methylprednisolone (MP) and prednisolone (PRED)) were administered in clinically relevant doses and combinations. Their levels were measured repeatedly in blood samples from the extracorporeal circulation over 6 h following administration. Population pharmacokinetic modeling analysis (NONMEM® 7.5) was performed.

Negligible clearance was observed for PRED and BAS. For all other substances, a saturable adsorption sub-model with linear decrease of the adsorption effect over the adsorbed amount best described the measured concentrations. The maximum absolute adsorbed amounts (95% CI) for TAC, CYA, MMF, EVER, and MP were 0.040 (0.028-0.053), 1.15 (0.39-1.91), 4.17 (2.00-6.35), 0.0163 (0.007-0.026), and 53.4 mg (20.9-85.9), respectively, indicating an adsorption of less than 5% of the daily administered dosages for all investigated substances.

In this large animal model, CytoSorb® hemoperfusion appears to have a limited effect on the clearance of tested ID.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.