Extracorporal Cytokin Removal in Septic Shock: a Prospective, Randomized, Multicenter Clinical Trial

Dosing of Extracorporeal Cytokine Removal In Septic Shock (DECRISS): a Prospective, Randomized, Multicenter Clinical Trial

Sepsis and septic shock have mortality rates between 20-50%. When standard therapeutic measures fail to improve patients' condition, additional therapeutic alternatives are applied to reduce morbidity and mortality. One of the most recent alternatives is extracorporeal cytokine hemoadsorption. One of the most tested devices is CytoSorb, however, there are a lot of open questions, such timing, dosing and of course its overall efficacy. This study aims to compare the efficacy of standard medical therapy (Group A, SMT) and continuous extracorporeal cytokine removal with CytoSorb therapy in patients with early refractory septic shock. Furthermore, we compare the dosing of CytoSorb adsorber device - as the cartridge will be changed in every (12 Group B) or 24 hours (Group C).

Inclusion Criteria:

• Septic shock as defined by the Sepsis-3 criteria
• Septic shock both medical or surgical ethiology (except for re-operation)
• APACHE > 25
• Mechanical ventilation
• Norepinephrine requirement ≥0.4 µg/kg/min for at least 30 minutes, when hypovolemia is highly unlikely as indicated by invasive hemodynamic measurements assessed by the attending physician
• Invasive hemodynamic monitoring to determine cardiac output and derived variables
• Procalcitonin level ≥ 10 ng/ml
• Inclusion within 6 - 24 hours after the onset of vasopressor need and after all standard therapeutic measures have been implemented without clinical improvement (i.e.: the shock is considered refractory)

Exclusion Criteria:

• Patients under 18 years and over 80
• Lack of health insurance
• Pregnancy
• Standard guideline-based medical treatment not exhausted (detailed below at 3.6) standard medical therapy)
• End stage organ failure
• New York Heart Association Class IV.
• Chronic renal failure with eGFR < 15 ml/min/1,73 m2
• End-stage liver disease (MELD score >30, Child-Pugh score Class C
• Unlikely survival for 24 hours according to the attending physician
• Acute onset of hemato-oncological illness
• Post cardiopulmonary resuscitation care
• Re-operation in context with the septic insult
• Immunosuppression
• systemic steroid therapy (>10 mg prednisolon/day)
• immunosuppressive agents (i.e.: methotrexate, azathioprine, cyclosporin, tacrolimus, cyclophosphamide)
• Human immunodeficiency virus infection (active AIDS): HIV-VL > 50 copies/mL
• Patients with transplanted vital organs
• Thrombocytopenia (<20.000/ml)
• More than 10%-of body surface area with a third-degree burn
• Acute coronary syndrome