Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and carries a risk for lethality, considerably exceeding that of a mere infection. Intensive care unit (ICU) mortality in patients with septic shock and acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) remains high and approximates 50-60% despite recent technical advancements in patient care. Sepsis is the leading etiology for AKI and CRRT requirement in ICU patients and almost half of the critically ill patients with sepsis develop AKI.~In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral pro-inflammatory mediators. These pro-inflammatory mediators and cytokines exert cellular toxicity and promote the development of organ dysfunction and increased mortality. Septic shock is defined according to the Sepsis-3 consensus criteria as sepsis with a vasopressor requirement to maintain a mean blood pressure (MAP) ≥65 mm Hg, despite adequate fluid resuscitation, and a serum lactate level >2 mmol/L.~In addition to treating AKI, CRRT techniques can be employed for adsorption of inflammatory mediators extracorporally using specially developed adsorption membranes, hemoperfusion sorbent cartridges or columns. The aim of these techniques is to decrease the early deleterious effects of the cytokine storm and high endotoxin levels during the first hours and days of treatment of septic shock to benefit the patient. Several methods and devices, such as Oxiris®-AN69 membrane, CytoSorb® cytokine hemoadsorption and polymyxin B (Toraymyxin) endotoxin adsorption and plasmapheresis have been evaluated in small study series or are under evaluation for improving patient outcomes in septic shock. However, to date the data on outcome benefits remains controversial. Previous study series have shown a decrease in cytokine levels, improved hemodynamics and diminished need for vasopressor in patients treated using these methods. However, mortality benefit remains unclear.~HA380 (Jafron Biomedical Co , Ltd, Zhuhai, China) is a CE-labeled hemoadsorption cartridge developed to treat patients with septic shock. It contains hemo-compatible, porous polymeric beads that adsorp cytokines and mid-molecular weight toxins on their surface. The cytokines absorved using this cartridge are IL-1, IL-6, IL-8, IL-10 in addition to TNF-α8.~Therefore, this study aims to examine the potential effects of cytokine adsorption using HA380 in addition to hemodiafiltration with the Oxiris®-AN69 membrane on ICU- and 90-day mortality in patients with septic shock. To study patients with the highest degree of morbidity the study will recruit only septic shock patients with a high vasopressor requirement before CRRT initiation.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Intensive care unit (ICU) mortality in patients with septic shock and acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) remains high and approximates 50-60%. Sepsis is the leading etiology for AKI and CRRT requirement in ICU patients.~In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral pro-inflammatory mediators. These pro-inflammatory mediators and cytokines exert cellular toxicity and promote the development of organ dysfunction and increased mortality.~In addition to treating AKI, CRRT techniques can be employed for adsorption of inflammatory mediators extracorporally using specially developed adsorption membranes, hemoperfusion sorbent cartridges or columns. Several methods and devices, such as Oxiris®-AN69 membrane, CytoSorb® cytokine hemoadsorption and polymyxin B (Toraymyxin) endotoxin adsorption and plasmapheresis have been evaluated in small study series but to date the data on outcome benefits remains controversial.~HA380 (Jafron Biomedical Co , Ltd, Zhuhai, China) is a CE-labeled hemoadsorption cartridge developed to treat patients with septic shock. It contains hemo-compatible, porous polymeric beads that adsorp cytokines and mid-molecular weight toxins on their surface. The cytokines absorved using this cartridge are IL-1, IL-6, IL-8, IL-10 in addition to TNF-α8.~Therefore, this study aims to examine the potential effects of cytokine adsorption using HA380 in addition to hemodiafiltration with the Oxiris®-AN69 membrane on ICU- and 90-day mortality in patients with septic shock and AKI.