Impact of extracorporeal membrane oxygenation (ECMO) support on piperacillin exposure in septic patients: a case-control study.

P Fillâtre, F Lemaitre, N Nesseler, M Schmidt, S Besset, Y Launey, A Maamar, P Daufresne, E Flecher, Y Le Tulzo, J M Tadie, P Tattevin

Journal: The Journal of antimicrobial chemotherapy 2021;76(5):1242-1249

PMID: 33569597

Abstract

OBJECTIVES

To describe the impact of extracorporeal membrane oxygenation (ECMO) devices on piperacillin exposure in ICU patients.

METHODS

This observational, prospective, multicentre, case-control study was performed in the ICUs of two tertiary care hospitals in France. ECMO patients with sepsis treated with piperacillin/tazobactam were enrolled. Control patients were matched according to SOFA score and creatinine clearance. The pharmacokinetics of piperacillin were described based on a population pharmacokinetic model, calculating the proportion of time the piperacillin plasma concentration was above 64 mg/L (i.e. 4× MIC breakpoint for Pseudomonas aeruginosa).

RESULTS

Forty-two patients were included. Median (IQR) age was 60 years (49-66), SOFA score was 11 (9-14) and creatinine clearance was 47 mL/min (5-95). There was no significant difference in the proportion of time piperacillin concentrations were ≥64 mg/L in patients treated with ECMO and controls during the first administration (P = 0.184) or at steady state (P = 0.309). Following the first administration, 36/42 (86%) patients had trough piperacillin concentrations <64 mg/L. Trough concentrations at steady state were similar in patients with ECMO and controls (P = 0.535). Creatinine clearance ≥40 mL/min was independently associated with piperacillin trough concentration <64 mg/L at steady state [OR = 4.3 (95% CI 1.1-17.7), P = 0.043], while ECMO support was not [OR = 0.5 (95% CI 0.1-2.1), P = 0.378].

CONCLUSIONS

ECMO support has no impact on piperacillin exposure. ICU patients with sepsis are frequently underexposed to piperacillin, which suggests that therapeutic drug monitoring should be strongly recommended for severe infections.

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: [email protected].

Address: St Brieuc Hospital, Réanimation Polyvalente, F-22000 St Brieuc, France.; Univ Rennes, Rennes University Hospital, Inserm, EHESP, Irset (Institut de Recherche en santé, Environnement et Travail) - UMR_S 1085, F-35000 Rennes, France.; Rennes University Hospital, Service de Réanimation de Chirurgie Cardiothoracique et de Chirurgie Vasculaire, F-35000 Rennes, France.; Univ Rennes, Inra, Inserm, Institut NUMECAN - UMR_A 1341, UMR_S 1241, CIC 1414, F35000 Rennes, France.; Sorbonne Université, Institute of Cardiometabolism and Nutrition, APHP, Pitié-Salpêtrière Hospital, Medical Intensive Care Unit, Paris, France.; Louis Mourier Hospital, Médecine Intensive-Réanimation, AP-HP, F92700 Colombes, France.; Rennes University Hospital, Surgical Critical Care Unit, Department of Anaesthesia, Critical Care and Perioperative Medicine, F-35033 Rennes, France.; Rennes University Hospital, Infectious Diseases and Intensive Care Unit, F-35033 Rennes, France.; Univ Rennes, Faculté de Médecine, Biosit, F-35043 Rennes, France.; Univ Rennes, Inserm-CIC-1414, IFR 140, F-35033 Rennes, France.; Rennes University Hospital, Haematology Unit, F-35033 Rennes, France.; Rennes University Hospital, Department of Thoracic and Cardiovascular Surgery, F-35033 Rennes, France.; Univ Rennes, Inserm U1099, Signal and Image Treatment Laboratory (LTSI), F-35033 Rennes, France.
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