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. Current suggested best practice for use of cytokine hemadsorption in sepsis.

To determine the clinical effect of continuous hemoperfusion with Cytosorb associated with standard Continuous Renal Replacement Therapy on hemodynamics and on clinically relevant outcome parameters in children with septic shock. Retrospective analysis. Pediatric intensive care unit. Eight consecutive children with septic shock who received hemoperfusion with Cytosorb while on Continuous Renal Replacement Therapy. Continuous hemoperfusion with Cytosorb (adsorber was changed every 24 h). Vasoactive-Inotropic Score was measured before and after the extracorporeal blood purification treatment. Bedside refractory septic shock score was calculated before the onset of the extracorporeal blood purification treatment. Time course of cytokines interleukin-6, interleukin-10, and tumor necrosis factor–alpha was measured at Time 0, then every 12 h until the end of blood purification treatment (72 or 96 h). Pediatric intensive care unit survival in our cohort was 90%. Median bedside refractory septic shock score was 2.1. Patients showed improved Vasoactive-Inotropic Score following blood purification (pre: 40.00 post: 8.89 p = 0.0076). Measurement of cytokines level showed a significant reduction of interleukin-6 plasma levels (7977.27–210.18 pg/mL, p = 0.0077) and interleukin-10 plasma levels (from 687.19 to 36.95 pg/mL, p = 0.0180). In those patients with detectable tumor necrosis factor–alpha plasma level, its reduction was not significant (p = 0.138). The median removal ratio was 80% for interleukin-6, 90% for interleukin-10, and 29% for tumor necrosis factor–alpha. The use of Cytosorb in combination with Continuous Renal Replacement Therapy as blood purification strategy in pediatric septic shock is associated with a rapid hemodynamic stabilization in the first 48 h of treatment and a significant reduction of interleukin-6 and interleukin-10.

Objectives: To describe a pediatric case of cytokine release syndrome secondary to chimeric antigen receptor-modified T cells associated with acute respiratory distress syndrome. Design: Case report. Setting: PICU. Patients: A 14-year-old boy with refractory B cell precursor acute lymphoblastic leukemia given chimeric antigen receptor cells developed severe cytokine release syndrome 7 days after the drug product infusion with progressive respiratory failure. He was admitted to PICU with a clinical picture of acute respiratory distress syndrome, requiring mechanical ventilation, and secondary hemophagocytic lymphohistiocytosis. Interventions: Hemoadsorption with cartridge column (Cytosorb) in combination with continuous renal replacement therapy was associated to the anti-cytokine therapy (tocilizumab, a monoclonal antibody targeting interleukin-6 receptor). Measurements and Main Results: Decrease of the inflammatory biomarkers (ferritin, interleukin-6, interleukin-10) in the first 96 hours associated with a progressive improvement of acute respiratory distress syndrome (Pao ₂/Fio ₂ ratio) 7 day after the start of the multimodal treatment. Conclusions: This case suggests that hemoadsorption with cartridge column in combination with continuous renal replacement therapy and tocilizumab is safe and potentially effective in pediatric patients with severe cytokine release syndrome.

Background: There is a lack of data to support the use of hemoadsorption in pediatric septic shock. The aim of our study was to assess the effectiveness and safety of CytoSorb therapy in this setting.Methods: Phase II interventional single arm pilot study in which 17 consecutive children admitted with septic shock who required continuous kidney replacement therapy (CKRT) and weighed ≥10 kg were included. A CytoSorb (CytoSorbents Inc, New Jersey, USA) hemoadsorption cartridge was added to the CKRT every 24 h for a maximum of 96 h. A control group of 13 children with septic shock treated with CKRT but not hemoadsorption at Children's Hospital Bambino Gesù and enrolled in the EuroAKId register was selected as an historical cohort. The primary outcome of the study was a reduction in vasopressor or inotrope dose of >50% from baseline by the end of CytoSorb therapy. Secondary outcomes included hemodynamic and biological changes, changes in severity scores, and 28-day mortality.Results: There were significant decreases in the Vasoactive Inotropic Score (VIS) and the Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score at 72 and 96 h from the start of the CytoSorb therapy compared to baseline; the reductions were larger in the hemoadsorption group than in the control group (historical cohort). 28-day mortality was lower, although not significantly, in the hemoadsorption group when compared to the control group (5/17 [29%] vs. 8/13 [61%] OR 0.26 [95% CI: 0.05–1.2]; p = 0.08).Conclusions: CytoSorb therapy may have some benefits in pediatric patients with septic shock. Future larger randomized trials are needed in this setting. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05658588, identifier (Clinicaltrials.gov NCT05658588).

Introduction: Sepsis-associated acute kidney injury (SA-AKI) represents a relevant cause of mortality and morbidity in critically ill children. Since with the “inflammatory theory” the authors have been witnessed an important role of inflammatory mediators in the pathophysiology and in the prognosis of SA-AKI, making the need of adjunctive therapies in association with kidney replacement therapies mandatory. Hemoperfusion with CytoSorb is a safe and well-tolerated therapy in septic shock: the very high surface area of the absorber means it is able to efficiently remove cytokines and other medium size molecules involved in cytokine storm, thus playing a synergistic effect with Continuous Kidney Replacement Therapy (CKRT).Materials and Methods: We retrospectively analyzed data from a cohort of eight critically ill children treated from January 2018 to March 2020 describing the impact of CKRT plus hemoperfusion with CytoSorb on renal outcome in critically ill children with septic shock.Results: We evidenced a significant reduction in interleukin (IL)-6 an IL-10 after hemoperfusion with CytoSorb in our pediatric population. Furthermore, we were able to show a significant improvement of creatinine and blood urea nitrogen (BUN) after blood purification and at pediatric intensive care units (PICU) discharge. We have observed a median of 2.5 CKRT days after stop of hemoperfusion (Q₁ 0.25; Q₃ 18.75). None of our patients required CKRT 30 days after PICU discharge (PICU-D). None of them developed CKD.Conclusion: Hemoperfusion with CytoSorb is a valuable therapeutic option in combination with CKRT in SA-AKI. More studies are warranted to confirm our results and in particular to define the role of this adjuvant therapy as a preemptive strategy to protect renal function in pediatric septic shock.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by a state of hyperinflammation. Blood purification techniques can blunt the inflammatory process with a rapidly relevant nonselective effect on the cytokine storm, thus potentially translating into survival benefit for these patients. In this cohort, we evaluated the impact of hemoadsorption with CytoSorb combined with continuous kidney replacement therapy used as adjunctive therapy in 6 critically ill children with multiple organ dysfunction due to HLH. In our series, we found a reduction in inflammatory biomarkers in patients with HLH secondary to infection. Ferritin, one of the most important bedside biomarkers of HLH, showed a reduction in most of the treated patients. The same results were found measuring interleukin-6 and interleukin-10. The same patients showed hemodynamic stabilization measured by the Vasopressor-Inotropic-Score, and reduction in the organ disease score measured with the Pediatric Logistic Organ Dysfunction score. In our cohort, mortality was less than expected based on the Pediatric Index of Mortality 3 score at pediatric intensive care unit admission. Our study shows that hemoperfusion could be a valuable therapeutic option in HLH: stronger scientific evidence is needed to confirm our preliminary experience.