Ilona Nowak-Kózka1,2, Kamil J Polok1, Jacek Górka1, Jakub Fronczek1, Anna Gielicz3, Bożena Seczyńska1, Mirosław Czuczwar4, Bartosz Kudliński5, Wojciech Szczeklik6. 1. Department of Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, ul. Skawińska 8, 31-066, Kraków, Poland. 2. Human Nutrition Department, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, ul. Grzegórzecka 20, 31-531, Kraków, Poland. 3. Department of Internal Medicine, Jagiellonian University Medical College, ul. Skawińska 8, 31-066, Kraków, Poland. 4. 2nd Department of Anesthesiology and Intensive Care, Medical University of Lublin, ul. Staszica 16, 20-081, Lublin, Poland. 5. Department of Teaching Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, ul. Fredry 10, 61-701, Poznań, Poland. 6. Department of Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, ul. Skawińska 8, 31-066, Kraków, Poland. wojciech.szczeklik@uj.edu.pl.
Abstract
BACKGROUND: The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD). METHODS: The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD. RESULTS: The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97-134 points) and 19.5 points (IQR 18-21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined. CONCLUSIONS: The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury.
BACKGROUND: The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD). METHODS: The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD. RESULTS: The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97-134 points) and 19.5 points (IQR 18-21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined. CONCLUSIONS: The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury.
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