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Pharmacokinetic Changes and Influencing Factors of Polymyxin B in Different ECMO Modes
Mi Xu1, Na Chen2, Yong-Wei Yu1
1Department of Critical Care Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Purpose:
With the development of extracorporeal membrane oxygenation (ECMO) technology, the duration of ECMO support has gradually increased, leading to an increased risk of ECMO-related bacterial resistance. Polymyxin B (PMB) is used to treat drug-resistant bacterial infections. However, the pharmacokinetic (PK) parameters of antibiotics may change during ECMO, resulting in over- or under-exposure. This study aimed to clarify the changes in PK parameters and identify factors influencing PMB levels in patients receiving venovenous or venoarterial ECMO.
Patients And Methods:
A prospective PK study was performed in 11 patients receiving ECMO with resistant bacteria. After reaching a steady state, the drug concentrations of PMB pre- and post-oxygenator were measured. Nonlinear mixed-effects modelling was used to construct a population PK model for PMB. Microbial results were assessed using repeated cultures at the end of treatment. Semiquantitative microbial culture results were used to form clearance and uncleared groups.
Results:
The PMB concentrations were not significantly different between pre- and post-oxygenator. A two-compartment model best described the PK of PMB. ECMO flow rate was included as a covariate of clearance (CL). Continuous renal replacement therapy (CRRT) were included as covariates on the volume of the central compartment. The PK parameters central compartment, volume of the peripheral compartment, CL, and inter-compartmental clearance or flow rate(Q) were 20.41 L, 9.86 L, 3.75 L/h, and 3.82 L/h. 7 patients (63.64%) had two consecutive negative bacterial cultures at discharge. The Css,avg shows a significant difference between clearance group (2.26±0.72) and uncleared group (1.25±0.24), P<0.05.
Conclusion:
There were no significant differences in PMB concentrations between pre- and post-oxygenator. The PK of PMB may be altered in patients receiving CRRT-ECMO. The ECMO flow rate is strongly correlated with the CL. The Css,avg is correlated with the bacterial clearance rate. In clinical practice, increasing the incidence of therapeutic drug monitoring may improve the clinical outcomes.
Insights
Polymyxin B levels during extracorporeal membrane oxygenation (ECMO) were studied. ECMO flow rate and continuous renal replacement therapy impact Polymyxin B pharmacokinetics, influencing bacterial clearance.
Area of Science:
- Pharmacokinetics
- Infectious Diseases
- Critical Care Medicine
Background:
- Extracorporeal membrane oxygenation (ECMO) support duration increases, raising risks of bacterial resistance.
- Polymyxin B (PMB) treats resistant infections, but its pharmacokinetics (PK) can change during ECMO, risking incorrect dosing.
- Understanding PMB PK during ECMO is crucial for effective treatment of drug-resistant bacterial infections.
Purpose of the Study:
- To investigate changes in Polymyxin B (PMB) pharmacokinetic parameters during ECMO.
- To identify factors influencing PMB levels in patients on venovenous or venoarterial ECMO.
- To correlate PMB concentrations with bacterial clearance in ECMO patients.
Main Methods:
- A prospective pharmacokinetic study involving 11 ECMO patients with resistant bacteria.
- Measurement of PMB concentrations pre- and post-oxygenator at steady state.
- Development of a population PK model using nonlinear mixed-effects modeling and analysis of microbial culture results.
Main Results:
- PMB concentrations did not significantly differ pre- and post-oxygenator.
- A two-compartment model described PMB PK, with ECMO flow rate affecting clearance (CL) and CRRT affecting central volume.
- Higher average steady-state concentrations (Css,avg) correlated with successful bacterial clearance.
Conclusions:
- PMB concentrations are stable across the ECMO oxygenator.
- Continuous renal replacement therapy (CRRT) may alter PMB pharmacokinetics in ECMO patients.
- Therapeutic drug monitoring of PMB is recommended to optimize clinical outcomes in ECMO patients.
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