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Published on: January 12, 2024
Dose Optimization of Vancomycin in Pediatric Post-Cardiac Surgery Patients: A Population Pharmacokinetic Modeling
J Kamp1, D J E Wannet2, E P Buddingh3
1Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Insights
Optimized vancomycin dosing for pediatric cardiac surgery patients was achieved using a population pharmacokinetic model. This model, influenced by renal function and body weight, enables precision dosing for improved treatment outcomes.
Area of Science:
- Pharmacology
- Pediatric Critical Care
- Antibiotic Stewardship
Background:
- Vancomycin is crucial for severe gram-positive infections.
- Optimizing vancomycin dosing in pediatric intensive care unit (PICU) patients post-cardiac surgery remains challenging.
- Factors like altered fluid status, renal function, and ECMO complicate dosing.
Purpose of the Study:
- To characterize vancomycin pharmacokinetics (PK) in pediatric cardiac surgery patients.
- To refine vancomycin dosing strategies for this population.
- To evaluate the model's utility for model-informed precision dosing (MIPD).
Main Methods:
- Retrospective cohort study of 193 PICU patients (Jan 2020-Dec 2023).
- Developed a 2-compartmental population PK model using NONMEM.
- Assessed covariates including renal function and body weight (BW); used Monte Carlo simulations for dose optimization.
Main Results:
- 193 patients and 706 vancomycin samples analyzed.
- Renal function and BW significantly impacted vancomycin PK.
- Non-linear dosing algorithm with lower per kg dose for higher BW suggested as optimal.
Conclusions:
- A population PK model for vancomycin in pediatric cardiac surgery patients was successfully developed.
- Serum creatinine and BW are key determinants of vancomycin PK.
- The model supports model-informed precision dosing for improved vancomycin therapy in this cohort.
Background And Objective:
Vancomycin is a glycopeptide antibiotic used for the treatment of severe gram-positive infections. Despite decades of clinical experience, optimized dosing for vancomycin in pediatric populations still warrants further investigation. Patients admitted to the pediatric intensive care unit (PICU) after cardiac surgery are often treated with vancomycin in case of (suspected) infection. However, vancomycin dosing in this population is often challenging due to fluctuations in volume status, (temporarily) compromised renal function or the use of diuretics or extracorporeal membrane oxygenation (ECMO). The main objective of this study was to describe vancomycin pharmacokinetics (PK) in pediatric cardiac surgery patients. Secondary objectives were to potentially optimize vancomycin dosing and to assess the suitability of the model to be used for model informed precision dosing (MIPD).
Methods:
A retrospective cohort study was performed with patients admitted to the PICU of the Leiden University Medical Center. Clinical data from post-cardiac surgery PICU patients receiving intravenous vancomycin between January 2020 and December 2023 were included in the analysis. Patients received vancomycin 10 mg/kg 4 times daily (qid), after which a trough concentration was generally sampled just before the fourth dose. Pharmacokinetic data were used to develop a population PK model by using a non-linear mixed effects modeling approach (NONMEM). In addition, potential covariates such as renal function, body weight (BW) and post-menstrual age were tested. The final model was used for vancomycin dose optimization using Monte Carlo simulations.
Results:
In total, 193 pediatric post-cardiac surgery patients, contributing a total of 706 vancomycin blood samples were included. The 2-compartmental population PK model best described the data. Renal function and BW were identified as significant and clinically relevant covariates on vancomycin PK. Model parameters were: elimination clearance: 4.01 L/min at 70 kg; intercompartmental clearance: 0.425 L/min at 70 kg; central volume of distribution: 56.1 L/70 kg; and peripheral volume of distribution: 21.7 L/70 kg (fixed). Dose simulations suggested a non-linear dosing algorithm, with relatively lower per kg dose for increasing BW to be optimal for our population. Furthermore, the model was considered to be suitable for the (a posteriori) prediction of future vancomycin serum concentrations.
Conclusion:
We successfully developed a population PK model for vancomycin in post-cardiac surgery children. Vancomycin PK were shown to be significantly influenced by serum creatinine and BW. Furthermore, we suggest a new vancomycin dosing regimen based on allometric scaling. The developed PK model can be used for model informed precision dosing of vancomycin in pediatric post-cardiac surgery patients.
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