Clinical and Immunologic Effects of Extracorporeal Cytokine Removal in Patients with Septic Shock: A Randomized Controlled Trial

BACKGROUND: Immune dysregulation and excessive cytokine release characterize the early phase of septic shock. Extracorporeal hemoadsorption with the CytoSorb device aims to restore immune balance by removing inflammatory mediators. Currently, clinical benefits remain uncertain. METHODS: In a single-center randomized controlled trial, 31 adult patients with septic shock, extracorporeal circuit, and interleukin-6 >500 pg/mL were included. The control group received standard care according to sepsis guidelines. The intervention group received standard care plus CytoSorb hemoadsorption. The primary outcome was the cumulative norepinephrine dose over 72 hours. Secondary outcomes included clinical and immunological endpoints. RESULTS: Between February 2022 and July 2023, 58 patients with septic shock and hyperinflammation were screened for study inclusion. Seventeen patients were randomized to the control group, and 14 patients received extracorporeal cytokine removal. Hemoadsorption started within 24 hours after the onset of septic shock in 93% of cases. The cumulative norepinephrine dose in 72 hours was 78 mg (52.7-117.8 mg) in the control group and 100.7 mg (66.4-190.8 mg) with extracorporeal cytokine removal ( P = 0.09). The total vasopressor dose per hour alive in the first 72 hours was significantly lower in the control group compared with extracorporeal hemoadsorption (1.2 mg, 0.8-2.0 mg vs . 2.5 mg, 1.7-3.3 mg; P = 0.0053). Survival at 48 hours (100%, n = 17/17 vs . 64 %, n = 9/14; P = 0.01) and 72 hours (94%, n = 16/17 vs . 57%, n = 8/14; P = 0.03) after onset of septic shock was higher in the control group. Intensive care unit mortality, length of stay, duration of septic shock, and other clinical outcomes did not differ between the groups. The humoral immune response, including pro- and anti-inflammatory cytokines, was similar between groups. Compared with controls, patients with extracorporeal cytokine removal had significantly lower lymphocyte percentages during the first 3 days of septic shock (6.2%, 5.0% - 17.4% vs. 2.5%, 2.1% - 5.6%; P = 0.04), whereas leukocyte and lymphocyte subsets as well as cytotoxic capacities were not altered by hemoadsorption. CONCLUSIONS: Early initiation of extracorporeal hemoadsorption in patients with septic shock did not improve vasopressor requirements or clinical outcomes, and no effects on the immune response were observed.