Extracorporeal Cytokine Adsorption in Sepsis: Current Evidence and Future Perspectives

Abstract

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.

Keywords: cytokine storm; extracorporeal cytokine adsorption; inflammation; mortality; sepsis; septic shock.

Figure 1

A synopsis of sepsis/septic shock pathophysiology. Sepsis pathogenesis involves a dysregulated immune response, where the pathogen and host factors trigger an excessive inflammatory cascade (red line). A cytokine storm amplifies leukocyte, complement, and coagulation activation, leading to tissue injury. Concurrently, an anti-inflammatory response (blue line) with regulatory T cell expansion and apoptotic immune cells increases susceptibility to secondary infections. Note: CLR: C-type Lectin Receptor; IL: Interleukin; NK: Natural Killer; NLR: Nod-like Receptor; RIG: Retinoic Acid-Inducible Gene-I-Like Receptors; TLR: Toll-like Receptors; TNF- α: Tumor Necrosis Factor-Alpha.

Figure 2

Future directions of extracorporeal cytokine adsorption in sepsis: towards personalized treatment. This infographic illustrates the four core elements driving the future of extracorporeal cytokine adsorption in sepsis management: (1) biomarker-guided therapy, using biomarkers such as IL-6, cfDNA, mHLA-DR, and LPS to identify immune states and guide treatment initiation; (2) selective adsorption technologies, designed to target specific inflammatory or anti-inflammatory mediators, thereby minimizing off-target effects; (3) sepsis phenotyping, enabling the stratification of patients based on immune profiles (e.g., hyper-inflammatory vs. immunosuppressed); and (4) pharmacokinetic considerations, to optimize therapy while avoiding unintended adsorption of essential medications. Together, these pillars support a precision medicine approach aiming to tailor extracorporeal therapy to individual patient needs. Note: Cell-free DNA; mHLA-DR: Monocyte human leukocyte antigen-DR; LPS: Lipopolysaccharide.