Search Results (14)

Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and life-threatening complication in critically ill children, contributing to high mortality rates (up to 30%) and long-term renal dysfunction in pediatric intensive care units. This review synthesizes recent advances in the signalling pathways underlying SA-AKI, emphasizing pediatric-specific mechanisms, biomarkers, and therapeutic targets. This review covers inflammatory cascades via TLR/NF-κB leading to cytokine storms (IL-6, TNF-α); apoptosis and necrosis involving mitochondrial Bcl-2 dysregulation and OLFM4; and emerging processes like pyroptosis (NF-κB-mediated), metabolic reprogramming (choline deficiency and Nrf2-mitophagy), and novel routes such as cGAS-STING and TGF-β signalling. Biomarkers like urinary OLFM4, DKK3, NGAL, and serum suPAR, alanine, and Penkid enable early diagnosis and risk stratification, with models like PERSEVERE-II enhancing prognostic accuracy. Therapeutic strategies include fluid optimization, renal replacement therapies (CRRT, SLED-f), and pathway-targeted interventions such as choline supplementation, oXiris for cytokine removal, Humanin for immunomodulation, and investigational cGAS-STING inhibitors. Despite progress, challenges persist in translating animal models to pediatric trials and addressing heterogeneity. Integrating multi-omics and precision medicine holds promise for improving outcomes, underscoring the need for multicenter studies in children. Full article

Aim: The rationale for combining various extracorporeal blood purification techniques to improve patient outcomes is currently being discussed extensively. The combined use of CytoSorb^®, with high capacity for cytokine removal, and Oxiris^®, which adsorbs endotoxins and smaller cytokines, may enhance the efficacy of blood purification in sepsis. Study Design: Retrospective analysis of efficacy and safety of simultaneous use of CytoSorb^® and Oxiris^® in 12 consecutive critically ill patients with COVID-19, who developed secondary bacterial sepsis and persistent hemodynamic instability. Results: Most of the patients (n = 8) treated with combination of the Oxiris^® and CytoSorb^® had a significant decrease in vasopressor requirement. Pre- and post-haemoadsorption data were analysed in 9 patients, who completed a 24 h course of treatment. A significant decrease in mean SOFA score (16.3 ± 1.7 to 15.0 ± 2.0 points), median vasopressor requirement (0.56 ± 0.29 to 0.11 ± 0.21 µg/kg/min), median procalcitonin levels (6.5 ± 27.0 to 1.6 ± 6.0 ng/mL), median IL-6 levels (584 ± 6279 to 107 ± 571 pg/mL), and mean leucocyte count (36.0 ± 20.6 to 20.9 ± 10.1 × 10³/mL) was observed. Furthermore, there was significant increase in PaO₂/FiO₂ ratio (108 ± 30 to 185 ± 55). We did not observe any device-associated adverse events or technical problems. A 27.5% drop in platelet count (269 ± 116 to 195 ± 82 × 10⁶/mL) and an 11.8% drop in haemoglobin level (10.7 ± 2.9 to 9.5 ± 2.0 g/dL) was noted. Conclusions: Our data suggests that combined use of Oxiris^® and CytoSorb^® for simultaneous cytokine and endotoxin removal in patients with underlying viral infection may be a promising therapeutic option. Our findings may serve as a guide for future research and provide directions for further development in this field. Full article

Background: Severe acute pancreatitis (SAP) presents with Multiple Organ Dysfunction Syndrome (MODS) in ~15% of cases, accounting for ~35% of early deaths within 48 h. Major complications—shock, renal failure, and respiratory insufficiency—arise from an overwhelming systemic inflammatory response driven by markedly elevated pro-inflammatory cytokines. Massive release of IL-2, IL-6, and TNF-α underlies the systemic inflammatory response syndrome (SIRS). Continuous veno-venous hemofiltration (CVVH) with the oXiris filter, adsorbing endotoxins and cytokines, has been used in sepsis and applied early in SAP to reduce cytokine load and organ injury. Aims: To evaluate the efficacy and safety of early CVVH with the oXiris filter in modulating the systemic inflammatory response by removing toxic cytokines from the bloodstream in patients with SAP complicated by organ dysfunction and refractory sepsis. Methods: This single-centre, retrospective, observational study was conducted at a tertiary university hospital between 2000 and 2022. Forty-eight consecutive patients with SAP at onset, defined according to the 2012 Atlanta Classification, with an APACHE II score ≥ 19 and persistent organ dysfunction (>48 h), were included. All patients were unresponsive to initial intensive care within the first 24 h and underwent urgent laparotomy with extensive peritoneal lavage, pancreatic necrosectomy, and placement of multiple abdominal drains, followed by transfer to the intensive care unit. CVVH (Prismax system) with the oXiris filter was initiated within 12 h post-surgery. IL-6 and TNF-α were selected as inflammatory markers and measured in both serum and ultrafiltrate at baseline (0 h) and at 24, 48, 72, and 96 h. These measurements were correlated with clinical parameters and prognostic scores (APACHE II, SOFA). Results: Treatment was well tolerated in all patients. The 28-day survival rate was 97.9%. There was a significant time-dependent decrease in IL-6 (p = 0.019) and TNF-α (p = 0.008) concentrations in the ultrafiltrate, consistent with high early adsorption followed by a reduced cytokine burden, whereas serum levels showed a non-significant downward trend (IL-6 p = 0.08; TNF-α p = 0.310). The APACHE II score decreased from 23 postoperatively to 8 by the second week (−65.2%; p = 0.013), with a statistically significant correlation between cytokine reduction and clinical improvement. Adverse events were rare and manageable. Conclusions: Early CVVH with the oXiris filter in SAP, complicated by MODS and refractory sepsis, proved safe, well-tolerated, and potentially effective in reducing cytokine burden and improving prognostic indices. These findings support the hypothesis of a relevant immunomodulatory effect, warranting prospective controlled trials to confirm its true impact on survival and organ recovery. Full article

Background: Sepsis and septic shock are major contributors to global morbidity and mortality. The “cytokine storm,” a hyper-inflammatory response, plays a central role in sepsis pathophysiology, leading to multi-organ failure. Extracorporeal cytokine adsorption therapies, such as CytoSorb, Toraymyxin, Oxiris, HA330/380, and Seraph 100 Microbind, aim to mitigate the inflammatory response by removing circulating cytokines and other mediators. Methods: A comprehensive search of Scopus and PubMed was conducted for studies published from January 2020 to May 2025. The search terms included “sepsis,” “septic shock,” and “extracorporeal cytokine adsorption.” Relevant studies, including clinical trials and meta-analyses, were included to assess the efficacy and safety of these therapies. Results: Extracorporeal cytokine adsorption has shown promising results in reducing cytokine levels, improving organ function, and decreasing vasopressor requirements. However, evidence regarding mortality reduction remains inconsistent. Studies have demonstrated benefits in sepsis, ARDS, and cardiogenic shock, improving organ recovery and inflammatory markers. Conclusions: Extracorporeal cytokine adsorption is a potential adjunctive therapy in sepsis management, offering improvements in organ function and inflammatory control. While the mortality benefit remains uncertain, ongoing research and large-scale clinical trials are essential to define its clinical role and optimize its application. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb^® and four Oxiris^® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb^® blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris^® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb^® and Oxiris^® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes. Full article

Critically ill patients with sepsis and severe COVID-19 are commonly characterized by a dysregulated immune response and an acute kidney injury. Continuous renal replacement therapy (CRRT) is now proposed as a promising adjuvant therapy to treat these critically ill patients by removing cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns from the blood. Although multiple hemofilters, including high-cutoff membranes, the oXiris hemofilter, the CytoSorb hemoadsorption device, and the Toraymyxin hemoperfusion cartridge, have been used in current clinical practice, the use of the oXiris hemofilter in critically ill patients is of particular interest because it is the only kind of hemofilter that can provide renal replacement therapy, remove endotoxins, and adsorb cytokines simultaneously. During the past five years, a growing body of literature has shown that CRRT with the oXiris hemofilter can improve hemodynamics and organ function and can decrease cytokines and endotoxins in both septic and COVID-19 patients. Here, we performed a narrative review to describe the development history of the oXiris hemofilter and to discuss the therapeutic effect of oXiris-CRRT on critically ill patients by searching the PubMed, Web of Science, and clinicaltrials.gov databases for articles published from inception to 8 September 2022 (updated on 1 November) with an English language restriction. We also summarized the current knowledge on anticoagulation techniques and safety concerns when delivering oXiris-CRRT sessions. Full article

Innate and adaptive immune system cells play a critical role in the host response to sepsis. Sepsis is a life-threatening disease characterized by apoptosis-induced depletion of immune cells and immunodepression, which contribute to morbidity and mortality. Many alterations in the expression of surface markers of neutrophils and monocytes have been described in septic patients. The aim of this study was to inspect the recently published literature to inform the clinician about the most up-to-date techniques for the study of circulating leukocytes. The impact on cell phenotypes and on the function of leukocytes of extracorporeal and non-blood purification treatments proposed for sepsis were also analyzed. We conducted a systematic review using Pubmed/Medline, Ovid/Willey, the Cochrane Library, the Cochrane Controlled Trials Register, and EMBASE, combining key terms related to immunological function in sepsis and selected the most relevant clinical trials and review articles (excluding case reports) published in the last 50 years. The most important alteration in neutrophils during sepsis is that they activate an anti-apoptotic survival program. In septic monocytes, a reduced characteristic expression of HLA-DR is observed, but their role does not seem to be significantly altered in sepsis. As regards adaptive immunity, sepsis leads to lymphopenia and immunosuppression in patients with septic shock; this process involves all types of T cells (CD4, CD8 and Natural Killer), except for regulatory T cells, which retain their function. Several promising therapies that target the host immune response are currently under evaluation. During the worldwide pandemic caused by SARS-CoV-2, it was useful to study the “cytokine storm” to find additional treatments, such as the oXiris^® filter. This therapy can decrease the concentration of inflammatory markers that affect the severity of the disease. Full article

Increased mortality has been observed in patients who develop acute kidney injury (AKI) in the setting of coronavirus disease 2019 (COVID-19), which has led to the approval of extracorporeal kidney support by the FDA. We analyzed the existing literature to compare the efficacy and therapeutic benefits of various extracorporeal modalities for the oXiris membranes and CytoSorb cartridge in high-flow continuous kidney replacement therapy (HFCKRT). AKI due to COVID-19 is mediated by a state of systemic inflammation (cytokine storm syndrome), leading to multiple organ dysfunction. Although there is no consensus on a protocol for providing kidney support therapy, clinically oriented studies have shown the capacities of oXiris and CytoSorb filters to effectively filter out pro-inflammatory components, leading to improved clinical outcomes in critically ill patients. In this review, we study the development of cytokine storm syndrome, important clinical evidence regarding the roles of various adsorption techniques in kidney support therapy in this setting, and a protocol influenced by FDA recommendations for oXiris and CytoSorb membranes. Full article

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris^®-AN69 membrane, CytoSorb^® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review. Full article