Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study

Abstract

Background: The aim of this proof of concept, prospective, randomized pilot trial was to investigate the effects of extracorporeal cytokine removal (CytoSorb®) applied as a standalone treatment in patients with septic shock.

Methods: 20 patients with early (<24 h) onset of septic shock of medical origin, on mechanical ventilation, norepinephrine>10 μg/min, procalcitonin (PCT) > 3 ng/mL without the need for renal replacement therapy were randomized into CytoSorb (n = 10) and Control groups (n = 10). CytoSorb therapy lasted for 24 h. Clinical and laboratory data were recorded at baseline (T₀), T₁₂, T₂₄, and T₄₈ hours.

Results: Overall SOFA scores did not differ between the groups. In the CytoSorb-group norepinephrine requirements and PCT concentration decreased significantly (norepinephrine: CytoSorb: T₀ = 0.54[IQR:0.20-1.22], T₄₈ = 0.16[IQR:0.07-0.48], p = .016; Controls: T₀ = 0.43[IQR:0.19-0.64], T₄₈ = 0.25[IQR:0.08-0.65] μg/kg/min; PCT: CytoSorb: T₀ median = 20.6[IQR: 6.5-144.5], T₄₈ = 5.6[1.9-54.4], p = .004; Control: T₀ = 13.2[7.6-47.8], T₄₈ = 9.2[3.8-44.2]ng/mL). Big-endothelin-1 concentrations were also significantly lower in the CytoSorb group (CytoSorb: T₀ = 1.3 ± 0.6, *T₂₄ = 1.0 ± 0.4, T₄₈ = 1.4 ± 0.8, *p = .003; Control: T₀ = 1.1 ± 0.7, T₂₄ = 1.1 ± 0.6, T₄₈ = 1.2 ± 0.6 pmol/L, p = .115). There were no CytoSorb therapy-related adverse events.

Conclusions: This is the first trial to investigate the effects of early extracorporeal cytokine adsorption treatment in septic shock applied without renal replacement therapy. It was found to be safe with significant effects on norepinephrine requirements, PCT and Big-endothelin-1 concentrations compared to controls.

Trial registration: The study has been registered on ClinicalTrials.gov, under the registration number of NCT02288975, registered 13 November 2014.

Keywords: CytoSorb; Cytokine removal; Cytokine storm; Extracorporeal blood purification; Hemoadsorption; Septic shock.