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Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery
Ralph Gertler1, Michael Gruber2, Gunther Wiesner3
1Klinik für Anaesthesie, operative und allgemeine Intensivmedizin, Notfallmedizin, Klinikum Links der Weser, University Medical Center Hamburg-Eppendorf, Bremen, Germany.
Insights
This study investigated cefuroxime (CXM) pharmacokinetics during cardiopulmonary bypass (CPB) in infants. Standard dosing is sufficient for prophylaxis, but continuous infusion optimizes cefuroxime (CXM) levels during cardiac surgery.
Area of Science:
- Pharmacology
- Pediatric Surgery
- Critical Care Medicine
Background:
- Limited data exist on cefuroxime (CXM) pharmacokinetics in infants under one year undergoing cardiopulmonary bypass (CPB).
- Understanding drug behavior during CPB is crucial for effective treatment in pediatric cardiac surgery.
Purpose of the Study:
- To evaluate the pharmacokinetic profile of cefuroxime (CXM) in pediatric patients less than one year of age during cardiac surgery with CPB.
- To determine optimal dosing strategies for cefuroxime (CXM) to maintain therapeutic concentrations.
Main Methods:
- A pharmacokinetic study involving 42 pediatric patients undergoing cardiac surgery.
- Cefuroxime (CXM) concentrations were measured using high-performance liquid chromatography after initial dosing and during CPB.
- Pharmacokinetic/pharmacodynamic (PK/PD) modeling was employed, considering body weight, CPB status, and postmenstrual age.
Main Results:
- Peak unbound cefuroxime (CXM) concentrations were higher during CPB compared to pre-CPB levels.
- A two-compartment model described cefuroxime (CXM) distribution, with systemic clearance, central and peripheral volumes of distribution identified.
- Simulations suggested a specific dosing regimen (25 mg/kg bolus + 5 mg/kg/h infusion) to maintain concentrations above the minimum inhibitory concentration (MIC).
Conclusions:
- The standard cefuroxime (CXM) dosing regimen is adequate for surgical prophylaxis in this population.
- Continuous cefuroxime (CXM) infusion can achieve a higher percentage of time above the minimum inhibitory concentration (MIC), potentially enhancing efficacy.
Aims:
Very little data exist regarding the effect of cardiopulmonary bypass (CPB) on cefuroxime (CXM) pharmacokinetics in children less than one year of age.
Methods:
50 mg kg-1 CXM i.v. after induction were followed by 75 mg kg-1 into the CPB circuit. In 42 patients undergoing cardiac surgery, 15-20 samples were obtained between 5 and 360 min after the first dose. Total CXM concentrations were measured by high-performance liquid chromatography and a pharmacokinetic/pharmacodynamic (PK/PD) modelling was performed.
Results:
Using a fixed protein binding of 15.6% for CXM, peak plasma concentrations of unbound CXM were 229 ± 52 μg ml-1 after the first bolus and 341 ± 86 μg ml-1 on CPB. Nadir concentrations before CPB were 69 ± 20 μg ml-1 and six hours later decreased to 41 ± 19 μg ml-1 with and 24 ± 14 μg ml-1 without CPB. A two-compartment model was fitted with the main covariates body weight, CPB and postmenstrual age (PMA). PK parameters were as follows: systemic clearance, 5.15 [95% CI 4.5-5.8] l h-1 ; central volume of distribution, 11.25 [9.41-13.09] l; intercompartmental clearance, 18.19 [14.79-21.58] l h-1 ; and peripheral volume, 17.07 [15.7-18.5] L. ƒT > MIC of 32 μg ml-1 for an 8-h time period was between 70 and 100% (2.5-10 kg BW). According to our simulation, 25 mg ml-1 CXM as a primary bolus and into the prime plus a 5 mg kg-1 h-1 infusion maintain CXM concentrations continuously above 32 μg ml-1 .
Conclusions:
The routine dosing regimen provided was sufficient for prophylaxis, but continuous dosing can provide a higher percentage of ƒT > MIC.
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