Pharmacokinetics and Modelling of Beta-Lactam in Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO)

The use of antibiotic therapy is common in intensive care units and primarily involves beta-lactams. Its optimal implementation is made difficult by the pharmacokinetic changes inherent in critically ill patients (fluid resuscitation, use of catecholamines, shock state, organ dysfunctions, especially those involved in drug elimination, implementation of extracorporeal circulations...). It has been demonstrated that delayed initiation of appropriate antibiotic therapy in severe infections is an independent predictor of poor prognosis.

The current joint recommendations from the French Society of Anesthesiology and Intensive Care (SFAR) and the French Society of Pharmacology and Therapeutics (SFPT) formulated in 2018 have codified the implementation of beta-lactam antibiotic therapy in critically ill patients, specifying administration modalities, initial dosages, as well as pharmacological therapeutic monitoring methods (plasma monitoring of the administered molecule after 24-48 hours of administration in all patients for whom pharmacokinetic variability is expected) and target plasma concentrations. However, there are no recommendations on prescription modalities for patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

VA-ECMO is a salvage therapy for cardio-pulmonary support via extracorporeal circulation, used in severe cardiac or respiratory failures. The use of antibiotic therapy is common in these patients. Pharmacokinetic variability factors common to intensive care patients are then exacerbated (massive fluid resuscitation, haemodilution by extracorporeal circulation, adsorption of xenobiotics on the exchange membrane and circuit, intensity of organ failures) while the severity of the patient necessitates immediate optimal antibiotic therapy administration.

The literature on antibiotic pharmacokinetics in patients under VA-ECMO is scarce in the adult population. Two exploratory approaches with distinct objectives can be found:

A "fundamental" approach, aiming to define the pharmacokinetic parameters (apparent volume of distribution, elimination half-life...) specific to each molecule within this population and to compare them with those observed in a reference population.