Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane

Investigation of Immunothrombosis in Intensive Care Patients With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane

Sepsis remains a global scourge. Before the SARS-CoV-2 pandemic, the World Health Organization estimated approximately 49 million cases annually, resulting in 11 million deaths. Defined by dysregulated host response to infection, sepsis leads to vital organ failure. Renal dysfunction affects about half of ICU patients, necessitating extracorporeal renal replacement therapy in approximately 10% of cases, alongside coagulation system involvement typified by thrombocytopenia. Immunothrombotic phenomena are pivotal in sepsis pathophysiology, activating coagulation and disrupting immune responses. Microcirculatory impairment, mediated by neutrophils, monocytes, and platelets, worsens vital organ perfusion. Excessive production of Neutrophil Extracellular Traps (NETs) is implicated in microcirculatory compromise during sepsis.

Inclusion Criteria:

• Patients aged 18 years and older

• Admitted to the intensive care unit with septic shock, defined as an increase in the Sequential Organ Failure Assessment (SOFA) score of at least 2 points due to infection, requiring vasopressor drugs to maintain a mean arterial pressure (MAP) ≥ 65 mmHg, and a lactate level > 2 mmol/L (18 mg/dL) despite adequate fluid resuscitation

• Requiring renal replacement therapy according to consensus indications:

  • KDIGO stage 3 acute kidney injury with oliguria or anuria persisting for more than 72 hours
  • Urea > 40 mmol/L
  • Plasma potassium > 5.5 mmol/L despite medical treatment
  • pH < 7.15 (pure metabolic acidosis with PaCO2 < 30 mmHg or mixed acidosis with PaCO2 > 50 mmHg without the possibility of improving alveolar ventilation)
  • Acute pulmonary edema secondary to hydrosaline overload resulting in severe hypoxemia (oxygen flow > 5 L/min or FiO2 > 50% during mechanical ventilation to maintain SaO2 > 95%) despite diuretic therapy

• Receiving continuous renal replacement therapy with a high-adsorption membrane (oXiris membrane) or a conventional membrane (HF1400 membrane)

Exclusion Criteria:

• Known history of constitutional thrombopathy (Bernard Soulier disease, Glanzmann thrombasthenia, Gray's syndrome or dense granule disease)
• Myelodysplastic or myeloproliferative syndrome
• Autoimmune thrombocytopenic purpura
• Acute leukemia
• Hemorrhagic shock
• Platelet transfusion within 7 days prior to inclusion
• Antiplatelet therapy with clopidogrel or ticagrelor within 5 days prior to inclusion, prasugrel or dipyridamole within 7 days prior to inclusion
• Active HIV infection or hepatitis B or C
• Pregnant woman
• Not affiliated to a social security system or not benefiting from such a system