Impact of renal replacement therapy strategy on beta-lactam plasma concentrations: the BETAKIKI study—an ancillary study of a randomized controlled trial

Annals of Intensive Care

Research

Dimitri Titeca-Beauport¹  Saad Nseir²  Didier Dreyfuss³  Nicolas Benichou³  Damien Roux⁴  Jean-Damien Ricard⁵  Bruno Mégarbane⁶  Nicolas Lerolle⁷  David Hajage⁸  Florence Tubach⁹  Julien Mayaux^1,10  Dorothée Carpentier^1,11  Nicolas de Prost^1,12  Laurent Martin-Lefèvre^1,13  Khaoula Mahjoub^1,14  Stéphane Gaudry^1,15  Eric Boulet^1,16 

[1] BoRealStudy Group, Medical Intensive Care Unit and EA7517, Amiens University Hospital, 80054, Amiens, France;Centre Médecine Intensive-Réanimation, CHU de Lille and INSERM U1285, Université de Lille, CNRS, UMR 8576-UGSF, 59000, Lille, France;DMU ESPRIT, Service de Médecine Intensive Réanimation, AP-HP, Université Paris Cité, Hôpital Louis Mourier, 92700, Colombes, France;Sorbonne Université, INSERM Unit S_1155 CORAKID, 75010, Paris, France;DMU ESPRIT, Service de Médecine Intensive Réanimation, AP-HP, Université Paris Cité, Hôpital Louis Mourier, 92700, Colombes, France;Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, 75015, Paris, France;DMU ESPRIT, Service de Médecine Intensive Réanimation, AP-HP, Université Paris Cité, Hôpital Louis Mourier, 92700, Colombes, France;Université Paris Cité, UMR1137 IAME, INSERM, 75018, Paris, France;Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Université Paris Cité, Paris, France;INSERM, UMRS-1144, Université Paris Cité, Paris, France;Département de Réanimation Médicale et Médecine Hyperbare, CHU Angers, Université d’Angers, Angers, France;Département de Santé Publique, Centre de Pharmacoépidémiologie (Céphépi), Unité de Recherche Clinique PSL-CFX, Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, CIC-1901, Paris, France;Département de Santé Publique, Centre de Pharmacoépidémiologie (Céphépi), Unité de Recherche Clinique PSL-CFX, Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, CIC-1901, Paris, France;Unité de Recherche Clinique, INSERM, UMR 1123, Paris, France;Médecine Intensive Réanimation, AP-HP, Hôpital Pitié-Salpétrière, 75013, Paris, France;Médecine Intensive Réanimation, Centre Hospitalier Universitaire Rouen, Rouen, France;Réanimation Médicale, AP-HP, Hôpital Henri Mondor, Créteil, France;Groupe de Recherche CARMAS, Université Paris-Est Créteil Val de Marne, 27010, Créteil, France;Réanimation Polyvalente, Centre Hospitalier Départemental - Site de La Roche-Sur-Yon, La Roche-sur-Yon, France;Organ Donation Service, Centre Hospitalier Universitaire de Nantes, Nantes, France;Service de Réanimation, Hôpital Delafontaine, 93200, Saint-Denis, France;Sorbonne Université, INSERM Unit S_1155 CORAKID, 75010, Paris, France;Médecine Intensive-Réanimation, AP-HP, Hôpital Avicenne, 93000, Bobigny, France;Val d’Oise, Hôpital René Dubos, Pontoise, France;

关键词: Acute kidney injury;    Beta-lactam;    Concentration;    Septic shock;    Renal replacement therapy;    Antibiotic;    Intermittent hemodialysis;    Hemofiltration;   

DOI  :  10.1186/s13613-023-01105-0

 received in 2022-11-15, accepted in 2023-02-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundSepsis prognosis correlates with antibiotic adequacy at the early phase. This adequacy is dependent on antibacterial spectrum, bacterial resistance profile and antibiotic dosage. Optimal efficacy of beta-lactams mandates concentrations above the minimal inhibitory concentration (MIC) of the targeted bacteria for the longest time possible over the day. Septic acute kidney injury (AKI) is the most common AKI syndrome in ICU and often mandates renal replacement therapy (RRT) initiation. Both severe AKI and RRT may increase outside target antibiotic concentrations and ultimately alter patient’s prognosis.Patients and methodsThis is a secondary analysis of a randomized controlled trial that compared an early RRT initiation strategy with a delayed one in 620 critically ill patients undergoing severe AKI (defined by KDIGO 3). We compared beta-lactam trough concentrations between the two RRT initiation strategies. The primary outcome was the proportion of patients with sufficient trough plasma concentration of beta-lactams defined by trough concentration above 4 times the MIC. We hypothesized that early initiation of RRT could be associated with an insufficient antibiotic plasma trough concentration compared to patients allocated to the delayed strategy.ResultsOne hundred and twelve patients were included: 53 in the early group and 59 in the delayed group. Eighty-three patients (74%) had septic shock on inclusion. Trough beta-lactam plasma concentration was above 4 times the MIC breakpoint in 80.4% (n = 90) of patients of the whole population, without differences between the early and the delayed groups (79.2% vs. 81.4%, respectively, p = 0.78). On multivariate analysis, the presence of septic shock and a higher mean arterial pressure were significantly associated with a greater probability of adequate antibiotic trough concentration [OR 3.95 (1.14;13.64), p = 0.029 and OR 1.05 (1.01;1.10), p = 0.013, respectively). Evolution of procalcitonin level and catecholamine-free days as well as mortality did not differ whether beta-lactam trough concentration was above 4 times the MIC or not.ConclusionsIn this secondary analysis of a randomized controlled trial, renal replacement therapy initiation strategy did not significantly influence plasma trough concentrations of beta-lactams in ICU patients with severe AKI. Presence of septic shock on inclusion was the main variable associated with a sufficient beta-lactam concentration.Trial registration: The AKIKI trial was registered on ClinicalTrials.gov (Identifier: NCT01932190) before the inclusion of the first patient.

【 授权许可】

CC BY   
© The Author(s) 2023

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