Clearance of Vasoactive Metabolites With Blood Purification

Critically Ill Patients

Intensive care, Septic shock, Inflammatory mediators, Renin Angiotensin System

Extracorporeal blood purification is a supportive therapy in the management of patients with sepsis or vasoplegic shock. The pathophysiology of sepsis is based on an inappropriate host response to infection. Certain medical devices with higher adsorption capacity make it possible to limit this inappropriate response and could thus improve the hemodynamics of patients in septic or vasoplegic shock. The preliminary experience of the investigators from clinical data of vasopressor withdrawal in pediatric patients treated with oXiris shows a 50% reduction in the vasopressor score, Vaso Inotropic Score (VIS), for 40% of patients within 24 hours following the start of treatment. Similar results were found in adult patients treated for severe COVID-19 or vasoplegic shock by the other centers participating in the study. Cytokine purification is an important physiological effect of purification membranes. However, this may not fully explain the rapid hemodynamic improvement of patients treated with an oXiris membrane. The role of angiotensin metabolites (Ang 1-5, 1-7, 1-9) in the systemic vascular tone of patients has been recently discussed. The administration of angiotensin 2 in vasoplegic shock in adults helps correct hypotension. In the group of patients with increased renin, this treatment was associated with a reduction in mortality. Indeed, increased renin associated with dysfunction of Angiotensin Converting Enzyme (ACE) leads to an accumulation of Angiotensin 1 which degrades to Ang 1-7. The hypothesis f the investigators is that the concentration of Ang 1 and Ang 1-7 is elevated in cases of vasoplegic shock and that the clearance of these vasodilator peptides by blood purification is associated with clinical improvement.

This is a pilot study, non-interventional research involving the human subjects, category 3, aimed at measuring the clinical and biological the clinical and biological effects of using the oXiris hemofiltration hemofiltration membrane. As part of the treatment: oXiris membrane hemofiltration with Prismaflex system, Phoxylium or Hémosol B0 dialysis solution, upper or lower dialysis catheter. Anticoagulation with heparin, citrate or none in case of severe haemostasis disorders. Treatment volume of 35 ml/kg/h maximum. For research purposes: collection of additional blood tubes (2 x 5mL heparinized tube) added to the usual samples, at the following times: Baseline (before starting treatment), under hemofiltration at 24h +/- 6h of treatment and at 72 hours +/- 12 hours. These samples will be analyzed by liquid chromatography - mass spectrometry / mass spectrometry (LC-MS/MS) by Attoquant diagnostics®, a laboratory specialized in analyses of the Renin-Angiotensin system. The angiotensins assayed are Angiotensin I, II, III and IV, as well as the intermediate peptides (1-5, 1-7, 1-9, 2-10, 2-7 and 3-7) and regulatory enzymes (renin, angiotensin converting enzyme, angiotensin 2-converting enzyme and neprilysin). Angiotensin metabolites have a very short half-life. Their depends on enzyme activity and degradation by circulating proteases. Two techniques are used to determine circulating concentration rapid treatment with protease inhibitors or the equilibrium technique. For the equilibrium technique, samples are incubated again to restore metabolite concentration prior to analysis. The samples at 3 time points (Baseline, H24 and H72) are analyzed using the equilibrium. The H24 sample will also be analyzed with a protease inhibitor pre-treatment. Patients will be monitored for 3 months (90-day mortality) using data collected collected in the course of care. Data from medical records and biological analyses will be entered into an eCRF. Data management will be carried out throughout the study, to enable baseline freezing and statistical analysis as early as possible after the end of the last patient's follow-up.

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