A Population Pharmacokinetic Analysis to Study the Effect of Extracorporeal Membrane Oxygenation on Cefepime Disposition in Children
| Autor: | Athena F, Zuppa, Nicole R, Zane, Ganesh, Moorthy, Heidi J, Dalton, Alan, Abraham, Ron W, Reeder, Joseph A, Carcillo, Andrew R, Yates, Kathleen L, Meert, Robert A, Berg, Anil, Sapru, Peter, Mourani, Daniel A, Notterman, J Michael, Dean, Marc R, Gastonguay |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Metabolic Clearance Rate Critical Illness medicine.medical_treatment Cefepime Population 030204 cardiovascular system & hematology Intensive Care Units Pediatric Critical Care and Intensive Care Medicine Models Biological Article 03 medical and health sciences Extracorporeal Membrane Oxygenation 0302 clinical medicine Pharmacokinetics medicine Extracorporeal membrane oxygenation Humans Renal replacement therapy education Oxygenator Volume of distribution education.field_of_study medicine.diagnostic_test business.industry Body Weight Infant 030208 emergency & critical care medicine Anti-Bacterial Agents surgical procedures operative Therapeutic drug monitoring Anesthesia Pediatrics Perinatology and Child Health Female business Protein Binding medicine.drug |
| Zdroj: | Pediatric Critical Care Medicine. 20:62-70 |
| ISSN: | 1529-7535 |
| DOI: | 10.1097/pcc.0000000000001786 |
| Popis: | Limited data exist on the effects of extracorporeal membrane oxygenation on pharmacokinetics of cefepime in critically ill pediatric patients. The objective was to describe cefepime disposition in children treated with extracorporeal membrane oxygenation using population pharmacokinetic modeling.Multicenter, prospective observational study.The pediatric and cardiac ICUs of six sites of the Collaborative Pediatric Critical Care Research Network.Seventeen critically ill children (30 d to2 yr old) on extracorporeal membrane oxygenation who received cefepime as standard of care between January 4, 2014, and August 24, 2015, were enrolled.None.A pharmacokinetic model was developed to evaluate cefepime disposition differences due to extracorporeal membrane oxygenation. A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data. The typical value of clearance in this study was 7.1 mL/min (1.9 mL/min/kg) for a patient weighing 5.8 kg. This value decreased by approximately 40% with the addition of renal replacement therapy. The typical value for V1 was 1,170 mL. In the setting of blood transfusions, V1 increased by over two-fold but was reduced with increasing age of the extracorporeal membrane oxygenation circuit oxygenator.Cefepime clearance was reduced in pediatric patients treated with extracorporeal membrane oxygenation compared with previously reported values in children not receiving extracorporeal membrane oxygenation. The model demonstrated that the age of the extracorporeal membrane oxygenation circuit oxygenator is inversely correlated to V1. For free cefepime, only 14 of the 19 doses (74%) demonstrated a fT_minimum inhibitory concentration of 16 mg/L, an appropriate target for the treatment of pseudomonal infections, for greater than 70% of the dosing interval. Pediatric patients on extracorporeal membrane oxygenation might benefit from the addition of therapeutic drug monitoring of cefepime to assure appropriate dosing. |
| Databáze: | OpenAIRE |
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