Techniques of extracorporeal cytokine removal: a systematic review of human studies

Background and aims: Hypercytokinemia is believed to be harmful and reducing cytokine levels is considered beneficial. Extracorporeal blood purification (EBP) techniques have been studied for the purpose of cytokine reduction. We aimed to study the efficacy of various EBP techniques for cytokine removal as defined by technical measures. Method: We conducted a systematic search for human clinical trials which focused on technical measures of cytokine removal by EBP techniques. We identified 41 articles and analyzed cytokine removal according to clearance (CL), sieving coefficient (SC), ultrafiltrate (UF) concentration and percentage removed. Results: We identified the following techniques for cytokine removal: standard hemofiltration, high volume hemofiltration (HVHF), high cut-off (HCO) hemofiltration, plasma filtration techniques, and adsorption techniques, ultrafiltration (UF) techniques relating to cardiopulmonary bypass (CPB), extracorporeal liver support systems and hybrid techniques including combined plasma filtration adsorption. Standard filtration techniques and UF techniques during CPB were generally poor at removing cytokines (median CL for interleukin 6 [IL-6]: 1.09 mL/min, TNF-alpha 0.74 mL/min). High cut-off techniques consistently offered moderate cytokine removal (median CL for IL-6: 26.5 mL/min, interleukin 1 receptor antagonist [IL-1RA]: 40.2 mL/ min). Plasma filtration and extracorporeal liver support appear promising but data are few. Only one paper studied combined plasma filtration and adsorption and found low rates of removal. The clinical significance of the cytokine removal achieved with more efficacious techniques is unknown. Conclusion: Human clinical trials indicate that high cut-off hemofiltration techniques, and perhaps plasma filtration and extracorporeal liver support techniques are likely more efficient in removing cytokines than standard techniques.