Elimination Clearance of Levosimendan (LVSMD) in Adult Patients in Cardiogenic Shock with Extracorporeal Membrane Oxygenation (ECMO)

The clearance (CL) of Lévosimendan (LVSMD) will be determined by the ratio of the total dose administered to the exposure characterised by the area under the curve (AUC) over time (CL=Dose/AUC). In order to obtain an accurate estimate of the AUC, blood samples will be taken from a catheter already in place for the patient's therapeutic needs and will be taken at 0, 2, 6, 24, 26 and 32 hours after the start of an intravenous infusion of LVSMD at the dosage defined according to the recommendations in the Summary of Product Characteristics (SmPC).

At enrollment visit, hour 1, 2 and 6 and at hour 24, 26 and 32 after enrollment visit

Success rate of weaning in the ECMO patient group

The success rate in the extracorporeal membrane oxygenation (ECMO) group will be assessed by the proportion of patients weaned from ECMO within 72 hours of the end of the levosimendan (LVSMD) infusion. ECMO weanability is assessed according to the Extracorporeal Life Support Organization (ELSO) guidelines by a weaning test, initiated after myocardial recovery, defined by a reduction in amine requirements to a minimum threshold to achieve a mean arterial pressure (MAP) \> 65 mmHg with an ECMO flow rate less than 2.5 L/min, usually performed for ECMO weaning. The weaning test is performed under an ECMO flow rate of 1L/min for 3 to 5 minutes, and is a success if the following parameters are obtained under low doses of amines: subaortic ITV \> 12 cm/s, LVEF \> 25-30%, absence of right ventricular dysfunction, central venous pressure \< 10 mmHg and MAP \> 60 mmHg

Hour 72 after enrollment visit

Hemodynamic success rate in the group without extracorporeal membrane oxygenation (ECMO)

he success rate in the group without extracorporeal membrane oxygenation (ECMO) will be assessed by the proportion of patients with an increase in cardiac index of at least 20% associated with venous oxygen saturation \> 65% within 72 hours following the end of the levosimendan (LVSMD) infusion, and/or improvement in hemodynamics (normalization of SvO2 and cardiac index \> 2.2 L/min/m2 without increase or introduction of dobutamine).

Hour 72 after enrollment visit

Population-based pharmacokinetic model of LVSMD and its metabolites

The population-based PK model, based on the results of the pediatric population study, will use a two-compartment model with first-order elimination for Lévosimendan (LVSMD). The appearance of metabolites will be modeled by transit compartments and their elimination will follow first-order kinetics. The collected clinical-biological data will be evaluated as covariates or as regressors (for time-dependent variables). Pharmacokinetic parameters will be evaluated according to a lognormal distribution (solutions \> 0) and regressors according to a normal distribution. Pharmacokinetic parameters will be calculated in a global structural population model and individual parameters will be determined by Bayesian estimation. The final model will then be used to perform simulations to establish the dosage allowing similar exposure between patients supported by extracorporeal membrane oxygenation (ECMO) and patients without extracorporeal membrane oxygenation (ECMO) during cardiogenic shock.

Hours 48, 72, 96, 120, 144, 168, 336 and 504 after enrollment visit

Influence of a change in intestinal microbiota on the conversion of levosimendan into its active metabolite

Given the metabolism of levosimendan to OR1896 by intestinal microbiota described in numerous studies, it seems legitimate to wonder whether inter-individual variability in response to treatment might not be linked to individual changes in intestinal microbiota. The aim is therefore to characterize the intestinal microbiota by swabbing and bioinformatic analysis, and to determine whether there are responder or non-responder profiles.

Two rectal swabs 24 hours apart, one at enrollment visit and one at hour 24 after enrollment visit