Effects of Hemoadsorption on Vascular Integrity in Septic Shock

Effects of Hemoadsorption on Vascular Integrity in Septic Shock (ADSORP-VIP Trial): Protocol of a Prospective, Randomised, Controlled Trial

This study aims to investigate the effects of adjunctive CytoSorb hemoadsorption therapy versus standard medical treatment on endothelial dysfunction in patients with refractory septic shock. The investigators hypothesize that hemoadsorption mitigates endothelial and glycocalyx injury by removing inflammatory mediators and other injurious circulating molecules, promoting hemodynamic stabilization.

This is a prospective, randomised, controlled, open-label, monocentric, proof-of-concept trial. Patients will be randomly assigned in a 1:1 ratio to receive either standard medical therapy alone or standard therapy plus continuous CytoSorb hemoadsorption for 24 hours. Blood samples will be collected at baseline, 6, 12, 18, and 24 hours, and then daily for 5 days to analyze endothelial markers, microRNAs, and inflammatory parameters. An adaptive group sequential design allows for an interim unblinded sample size re-estimation after the first 30 evaluable patients.

Inclusion Criteria:

• Septic shock as defined by Sepsis-3 criteria.
• Serum lactate levels >2 and <8 mmol/L at screening.
• Fluid unresponsiveness: Objectively confirmed via dynamic tests or fluid challenges following initial resuscitation.
• Vasopressor Dose Threshold: Norepinephrine base equivalent (NEE) dose > 0.5 µg/kg/min.
• Systemic corticosteroid treatment on board for at least 30 minutes.
• Tissue perfusion impairment: Persistently elevated serum lactate AND/OR prolonged capillary refill time (> 3 seconds) despite standard therapy.
• Alternative causes of shock (e.g., obstructive or cardiogenic) must be ruled out using critical care ultrasonography (CCUS).
• Arterial, central venous catheters and an invasive hemodynamic device (PiCCO, Getinge) in place.
• Inclusion within a maximum of 12 hours after the onset of vasopressor need.
• High likelihood of a dysregulated immune response (PCT ≥ 5 ng/mL AND/OR IL-6 ≥ 1000 pg/mL AND/OR Ferritin ≥ 1000 ng/mL).
• Written informed, retrospective or prospective consent.

Exclusion Criteria:

• Patients under 18 years of age and over 80.
• Unlikely to survive for 24 hours (Moribund).
• Pregnancy.
• SOFA-2 score ≥ 16 at ICU admission.
• Source control is uncertain.
• Thrombocytopenia (<20,000/µL).
• Criteria of standard guideline-based medical treatment not exhausted.
• End-stage organ failure (chronic renal failure (estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2), chronic liver failure (MELD Score >30, ChildPugh score class C.), chronic heart failure (New York Heart Association class IV.); severe chronic pulmonary disease (chronic obstructive pulmonary disease: GOLD D)).
• Expected need to disconnect CytoSorb therapy for more than 2 hours (e.g., surgery, CT transfer).