Alterations of the Renin-angiotensin-aldosterone System in sEptic Shock

Septic shock is a common and life-threatening condition associated with an in-hospital mortality rate exceeding 40%. The symptomatic management of septic shock relies primarily on vasopressor therapy, particularly norepinephrine. However, the use of high doses of norepinephrine may lead to adverse effects, prompting the search for alternative therapeutic strategies, including angiotensin II, which has recently been investigated as an adjunctive vasopressor. Indeed, alterations of the renin-angiotensin-aldosterone system (RAAS), particularly a relative deficiency of angiotensin II, have been hypothesized to occur during septic shock. However, to date, no human study has used gold-standard techniques for measuring RAAS peptides to confirm this hypothesis. Furthermore, it remains unclear whether these alterations are specific to septic shock or may also be observed in less severe infections (sepsis) or in other forms of circulatory failure, such as cardiogenic shock.

Inclusion Criteria: Adult patients with septic shock: * Proven or suspected infection. * Persistent arterial hypotension requiring norepinephrine administration to maintain a mean arterial pressure above 65 mmHg despite adequate fluid resuscitation. * Hyperlactatemia \> 2 mmol/L. Adult critically ill control patients with sepsis without circulatory failure: * Proven or suspected infection. * Absence of persistent arterial hypotension requiring norepinephrine administration to maintain a mean arterial pressure above 65 mmHg. * An increase of at least 2 points in the SOFA score attributable to infection. Adult critically ill control patients with cardiogenic shock: * Acute cardiac disease, such as myocardial infarction. * Persistent arterial hypotension requiring norepinephrine administration to maintain a mean arterial pressure above 65 mmHg despite adequate fluid resuscitation. * Low cardiac output: cardiac index \< 2.2 L/min/m² or the need for inotropic support (including norepinephrine) to maintain a cardiac index \> 2.2 L/min/m². * Elevated left ventricular filling pressures, measured invasively or estimated by echocardiography. * Hyperlactatemia \> 2 mmol/L. Adult healthy volunteers: * Absence of active or chronic disease. * Absence of long-term medication use. * No surgery or medication intake within the previous month. * Absence of ongoing pregnancy. * Non-smoker. Exclusion Criteria: * Patients deprived of liberty by judicial or administrative decision. * Patients admitted to the intensive care unit for more than 48 hours. * Patients previously enrolled in an interventional study with overlapping follow-up. * Patients benefiting from State Medical Aid (AME).