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Impact of MARS® therapy on piperacillin concentration in critically ill patients
Mémoire de Master / Thèse d'exercice   Open Access

Impact of MARS® therapy on piperacillin concentration in critically ill patients

Lucas Allegre
Masters , Université de Montpellier
18/10/2024

Résumé

Albumin dialysis MARS® Therapeutic drug monitoring Réanimation en hépatologie Dialyse Albumines Bêta-lactamines Pipéracilline Pharmacovigilance Association de pipéracilline et de tazobactam Intensive care units Beta-Lactams Piperacillin Surveillance des médicaments
Background: patients with acute liver failure (ALF) or acute on chronic liver failure (ACLF) are at high risk of sepsis or septic shock. Extracorporeal liver support systems such as MARS® therapy may increase the clearance of antimicrobial drugs. Underdosing of antimicrobial therapy could result in poor clinical outcome in these severely ill patients. The main objective of the study was to assess the impact of MARS® therapy on total piperacillin serum concentrations in critically ill patients. Methods: we conducted a retrospective, single-center study in France between March 2023 and July 2024. Patient treated with MARS® with a clinical indication of piperacillin-tazobactam were included in the study. The MARS® therapy was performed for 8-hour sessions on three consecutive days. Piperacillin-tazobactam was administered as a continuous infusion after an initiate loading dose. Blood samples were taken before and after each MARS® session to measure total piperacillin serum concentrations. A multivariate linear mixed model analysis was performed to assess the impact of MARS® sessions on total piperacillin serum concentrations. Results: seventeen patients, treated with piperacillin and MARS® therapy (total of 43 sessions) were included. The majority of patients suffered from alcoholic cirrhosis (83.3%) with a median MELD score of 34 [29-38] at admission. In the multivariate analysis of 75 piperacillin concentration measurements, we found a relative reduction in total piperacillin concentration of 42% [95% CI, -62; -23] (p<0.001), after one MARS® session. Number of sessions significantly decrease total piperacillin concentration by 19% [95% CI, -30; -9] (p<0.001) per new session. Additionally, 35.3% of patients exhibited at least one episode of underdosage in piperacillin after a MARS® session. Conclusion: total plasma piperacillin concentration is strongly impacted by a MARS® session. Number of sessions seems to increase this reduction. These results highlight the importance of personalizing antibiotic dosing strategies in patients treated with MARS®, in order to ensure optimal efficacy of antimicrobial treatment.

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