BACKGROUND: Sepsis is characterized by a dysregulated host response to infection and remains associated with substantial mortality. Extracorporeal blood purification strategies are explored as adjunctive approaches to modulate host-response dysregulation. OBJECTIVES: Practice-oriented overview of current extracorporeal immunomodulatory strategies in sepsis and septic shock and a summary of available evidence and guideline position. MATERIALS AND METHODS: Narrative review focusing on randomized trials, meta-analyses, guidelines, and ongoing study programs addressing nonselective hemoadsorption, selective endotoxin removal, and therapeutic plasma exchange. RESULTS: Evidence for nonselective hemoadsorption remains conflicting; recent higher-quality studies and guidelines do not show a proven clinical benefit and raise potential safety concerns. Selective endotoxin adsorption is biologically plausible and may be relevant in endotoxin-positive subgroups. Therapeutic plasma exchange is supported by mechanistic rationale, small randomized studies, and meta-analyses; confirmation in adequately powered multicenter trials is pending. CONCLUSION: Extracorporeal immunomodulation should not be regarded as a uniform intervention. Progress will depend on precise patient selection, biomarker-guided allocation, appropriate dosing, and structured implementation. Until robust outcome data are available, these therapies should be used cautiously and preferably in experienced centers or study frameworks.
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