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Published on: June 27, 2018
Meropenem extraction by ex vivo extracorporeal life support circuits
Christopher Cole Honeycutt1, Charles Griffin McDaniel1, Autumn McKnite2
1Duke University, Durham, North Carolina, USA.
Background:
Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem. The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction.
Methods:
Standard doses of meropenem were administered to three different configurations (n = 3 per configuration) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24 h. Similarly, standard doses of meropenem were administered to CRRT circuits (n = 4) and serial sampling was conducted over 4 h. Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation. Meropenem concentrations were quantified, and percent recovery was calculated for each sample.
Results:
Meropenem was cleared at a similar rate in ECMO circuits of different configurations (n = 3) and controls (n = 6), with mean (standard deviation) recovery at 24 h of 15.6% (12.9) in Complete circuits, 37.9% (8.3) in Oxygenator circuits, 47.1% (8.2) in Pump circuits, and 20.6% (20.6) in controls. In CRRT circuits (n = 4) meropenem was cleared rapidly compared with controls (n = 6) with a mean recovery at 2 h of 2.36% (1.44) in circuits and 93.0% (7.1) in controls.
Conclusion:
Meropenem is rapidly cleared by hemodiafiltration during CRRT. There is minimal adsorption of meropenem to ECMO circuit components; however, meropenem undergoes significant degradation and/or plasma metabolism at physiological conditions. These ex vivo findings will advise pharmacists and physicians on the appropriate dosing of meropenem.
Insights
Meropenem is rapidly cleared during continuous renal replacement therapy (CRRT) and minimally adsorbed to extracorporeal membrane oxygenation (ECMO) circuits. Findings inform meropenem dosing in critically ill patients requiring life support.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Critical Care Medicine
- Infectious Diseases
Background:
- Meropenem is a vital antibiotic for treating infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in critically ill patients.
- Many critically ill patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), necessitating an understanding of drug pharmacokinetics within these circuits.
- Physicochemical properties suggest minimal meropenem extraction by ECMO and rapid clearance by CRRT.
Purpose of the Study:
- To determine meropenem extraction in ex vivo ECMO and CRRT circuits.
- To elucidate the contribution of different ECMO circuit components to meropenem extraction.
- To provide data for optimizing meropenem dosing in patients on extracorporeal life support.
Main Methods:
- Standard meropenem doses administered to ex vivo ECMO (n=3) and CRRT (n=4) circuits.
- Serial blood sampling over 24 hours (ECMO) and 4 hours (CRRT).
- Control groups used to account for drug degradation; meropenem concentrations quantified, and percent recovery calculated.
Main Results:
- Meropenem clearance in ECMO circuits was similar to controls, with varying recovery rates across configurations (Complete: 15.6%, Oxygenator: 37.9%, Pump: 47.1%).
- CRRT circuits demonstrated rapid meropenem clearance compared to controls (2.36% recovery at 2 hours vs. 93.0% in controls).
- Minimal meropenem adsorption to ECMO components was observed, but significant degradation/metabolism occurred.
Conclusions:
- Meropenem undergoes rapid clearance during CRRT hemodiafiltration.
- ECMO circuits show minimal meropenem adsorption, but significant degradation/metabolism occurs under physiological conditions.
- These ex vivo findings are crucial for guiding meropenem dosing strategies in critically ill patients on ECMO and CRRT.
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