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Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome ARDS
Published on: September 7, 2016
Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during
Max Andresen1, Joaquin Araos2, Kwok-Yin Wong3
1Laboratory 103B, Centro de Investigaciones Médicas, Departamento de Medicina Intensiva, Facultad de Medicina y Hospital Clínico, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago 8330024, Chile. andresen@med.puc.cl.
Introduction:
The use of antibiotics is mandatory in patients during extracorporeal membrane oxygenation (ECMO) support. Clinical studies have shown high variability in the antibiotic concentrations, as well as sequestration of them by the ECMO circuit, suggesting that the doses and/or interval administration used during ECMO may not be adequate. Thus, a fast response sensor to estimate antibiotic concentrations in this setting would contribute to improve dose adjustments. The biosensor PenP has been shown to have a dynamic range, sensitivity and specificity useful for pharmacokinetic (PK) tests in healthy subjects. However, the use of this biosensor in the context of a complex critical condition, such as ECMO during acute respiratory distress syndrome (ARDS), has not been tested.
Objectives:
To describe, by using PenP Biosensor, the pharmacokinetic of meropenem in a 24-h animal ARDS/ECMO model.
Methods:
The PK of meropenem was evaluated in a swine model before and during ECMO.
Results:
The PK parameters such as maximum concentration (Cmax), elimination rate constant (Ke), and cleareance (Cl), were not significantly altered during ECMO support.
Conclusions:
(a) ECMO does not affect the PK of meropenem, at least during the first 24 h; and (b) PenP has the potential to become an effective tool for making medical decisions associated with the dose model of antibiotics in a critical patient context.
Insights
Extracorporeal membrane oxygenation (ECMO) does not alter meropenem pharmacokinetics in an animal model of acute respiratory distress syndrome (ARDS). The PenP biosensor shows potential for real-time antibiotic dose adjustments in critical care.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Biomedical Engineering
Background:
- Antibiotic dosing during extracorporeal membrane oxygenation (ECMO) is challenging due to concentration variability and circuit sequestration.
- Optimizing antibiotic therapy in critically ill patients requires precise pharmacokinetic (PK) monitoring.
- The PenP biosensor offers potential for rapid antibiotic concentration assessment.
Purpose of the Study:
- To evaluate the pharmacokinetics of meropenem during ECMO in an animal model of acute respiratory distress syndrome (ARDS).
- To assess the utility of the PenP biosensor for monitoring meropenem PK in this critical care setting.
Main Methods:
- Utilized a swine model to simulate ARDS and ECMO support.
- Measured meropenem pharmacokinetics (PK) before and during ECMO using the PenP biosensor.
- Analyzed key PK parameters including Cmax, Ke, and Cl.
Main Results:
- Meropenem's PK parameters (Cmax, Ke, Cl) remained statistically unchanged during ECMO support.
- The PenP biosensor demonstrated feasibility for PK assessment in an ARDS/ECMO model.
Conclusions:
- ECMO support does not significantly impact meropenem pharmacokinetics within the initial 24 hours.
- The PenP biosensor holds promise as a tool for guiding antibiotic dosing decisions in critically ill patients on ECMO.
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