The ECMOCYP (cytochromes P450 Activity) Study

The Geneva cocktail will be administered on 2 occasions at D3 after tMCS implantation (or start of the cardiogenic shock) and 14 days after tMCS explantation (or cardiogenic shock termination defined as: no need to use inortropic or vasopressive agent and absence of organ insufficiency)

Primary endpoint:

• Evaluate the impact of tMCS on the activity of CYPs as measured with metabolic ratios MRs (CYP activity at
• D3 post tMCS implantation and 14 days after tMCS explantation vs the activity of CYPs in the control group.

Secondary endpoints:

• Evaluate the correlation between the activity of CYPs and IL-6 levels
• Evaluate the correlation between the activity of CYPs and CRP levels
• Evaluate the correlation between the activity of CYPs and TNF-α levels
• Evaluate the correlation between the activity of CYPs and IL-1β levels
• Evaluate the correlation between the activity of CYPs and IFN-γ levels
• Compare CYP activity vs expected CYP activity based on patients' CYP genotyping
• Compare CYP activity between VA-EMCO and micro-axial pump device (Impella® CP)

Inclusion criteria

• Male and female patients presenting a refractory cardiogenic shock, requiring temporary mechanical circulatory support (tMCS), with either the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or a micro-axial pump device (Impella® CP).
• Male and female patients in cardiogenic shock according to the SCAI (Society for Cardiovascular Angiography and Interventions) ESC (European Society of Cardiology) definition and not requiring or not eligible to temporary mechanical circulatory support (tMCS). (e.g. ECMO, Impella®, intra-aortic balloon pump) (control group)
• Age > 18 years old
• Comprehension of French
• Ability to give consent (consent will be sought from the therapeutic representative or from relatives as the patient will be sedated and intubated. Definitive consent will be sought at patient's second blood sample planned after tMCS explantation (in case of patient's favorable outcome).

Exclusion criteria

• Male and female patients presenting a refractory ARDS requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO)
• Inability to receive the Geneva cocktail by enteral way
• Severe or terminal Renal impairment (defined as GFR<30ml/min according to Cockroft-Gault)
• Severe chronic hepatic insufficiency (CHILD B-C)
• Sensitivity to any of the drugs used in the Geneva Cocktail
• Intake of drugs altering CYPs activity (Strong inhibitor or inducer based on https://www.hug.ch/sites/hde/files/structures/pharmacologie_et_toxicologie_cliniques/a5_cytochromes_6_2.pdf)