Background: Hemoperfusion with the HA330/HA380 cartridge has markedly evolved during the past decade and has thus been widely used in intensive care settings to treat critical or hyperinflammatory illnesses. Numerous clinical studies have demonstrated that HA330/HA380 hemoperfusion might mitigate systemic inflammatory response syndrome and organ dysfunction in ICU patients by removing inflammatory mediators and metabolic toxins from the blood. However, there is currently lacking a systematic evaluation on the safety and efficacy of HA330/HA380 hemoperfusion in intensive care settings. Summary: We searched the PubMed database, Chinese Clinical Trial Registry, and ClinicalTrials.gov for articles published from inception to June 20, 2024 (updated on September 10, 2024) to perform a state-of-the-art review of HA330/HA380 hemoperfusion in daily critical care practice. We discuss the basic technique characteristics and ex vivo investigations of the HA330/HA380 cartridge and summarize the latest clinical evidence regarding the use of HA330/HA380 hemoperfusion for the treatment of sepsis, severe COVID-19, cardiac surgery, acute pancreatitis, liver failure, and blunt trauma. Ex vivo studies suggest that the HA330/HA380 cartridge demonstrates satisfactory biocompatibility and substantial adsorption capacity for inflammatory cytokines, such as interleukin-6, interleukin-10, and tumor necrosis factor-α. Small-scale clinical studies indicate that HA330/HA380 hemoperfusion may help reduce plasma levels of inflammatory mediators, alleviate organ dysfunction, and improve survival in some critically ill patients with sepsis, severe COVID-19, acute pancreatitis, and blunt trauma. Key Messages: (i) The HA330/HA380 cartridge contains abundant, coated, biocompatible sorbent beads made of styrene-divinylbenzene copolymers. (ii) HA330/HA380 hemoperfusion, with or without combined continuous renal replacement therapy, is a promising treatment option for some critically ill patients by removing proinflammatory mediators and alleviating organ dysfunction. (iii) The HA330/HA380 cartridge may adversely adsorb antibiotics, and appropriate antibiotic dosing adjustment and plasma drug level monitoring is recommended. (iv) There are currently numerous ongoing clinical trials evaluating the safety and efficacy of HA330/HA380 hemoperfusion in critically ill patients who develop sepsis or undergo cardiopulmonary bypass, which will certainly sharpen our future practice of HA330/HA380 hemoperfusion in ICU.

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