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Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?
Jennifer H Huang1, Rachel Sunstrom2, Myrna Y Munar3
1Division of Pediatric Cardiology, Doernbecher Children's Hospital, Oregon Health Science University, Portland, Ore.
Insights
Children undergoing cardiac surgery may not receive therapeutic cefuroxime antibiotic levels due to fluid dilution. A new nomogram predicts when these subtherapeutic levels occur, guiding timely redosing to reduce infection risk.
Area of Science:
- Pediatric Cardiac Surgery
- Pharmacokinetics
- Infectious Disease Prevention
Background:
- Perioperative antibiotics are crucial but do not eliminate postoperative infections.
- Cardiac surgery with cardiopulmonary bypass involves fluid shifts that can dilute antibiotic concentrations.
- Subtherapeutic antibiotic levels in children undergoing these procedures are a concern.
Purpose of the Study:
- To determine if children undergoing cardiac surgery with cardiopulmonary bypass receive subtherapeutic levels of perioperative antibiotics.
- To develop a predictive tool for identifying patients at risk of subtherapeutic antibiotic levels.
Main Methods:
- Utilized published pharmacokinetic data for cefuroxime.
- Developed a computer simulation model to predict cefuroxime plasma levels.
- Created a nomogram based on time from dosing and additional fluid volume administered.
Main Results:
- A 1-compartment pharmacokinetic model predicted cefuroxime levels for various doses and fluid volumes.
- Example: A 25-mg/kg dose with 275 mL/kg additional fluid becomes subtherapeutic (<16 mg/L) at 4 hours.
- The nomogram predicts all patients reach subtherapeutic levels by 8 hours, with higher fluid volumes leading to earlier subtherapeutic levels.
Conclusions:
- The developed model and nomogram can predict subtherapeutic cefuroxime levels in pediatric cardiac surgery patients.
- This tool assists in determining the need for additional antibiotic doses in patients receiving large fluid volumes.
- Rational antibiotic dosing may decrease postoperative infections in this high-risk population.
Objectives:
Perioperative antibiotics have decreased-but not eradicated-postoperative infections. In patients undergoing cardiac surgery with cardiopulmonary bypass, the dilutional effect of the priming and any additional volume given during the procedure may lead to subtherapeutic antibiotic levels. Our aim was to determine if children undergoing cardiac surgery with cardiopulmonary bypass receive perioperative antibiotics at subtherapeutic levels.
Methods:
Using published pharmacokinetic data on cefuroxime, we developed a computer simulation model to generate a nomogram predicting patients at risk for subtherapeutic cefuroxime levels based on time from initial dosing and additional volume given.
Results:
A computer-generated 1-compartment pharmacokinetic model was created to predict cefuroxime plasma levels over time for patients of all weights and additional volumes given for both a 25- and 50-mg/kg intravenous dose. For example, following a 25-mg/kg dose, a patient receiving an additional volume of 275 mL/kg is predicted to be subtherapeutic (<16 mg/L=4×minimum inhibitory concentration) at 4 hours. Our nomogram predicts all patients will be subtherapeutic at 8 hours, consistent with general pediatrics dosing schemes. Following a 50-mg/kg dose, levels are predicted to be subtherapeutic after an additional volume of 315 mL/kg at 5.5 hours.
Conclusions:
Our model predicts which patients undergoing cardiac surgery with cardiopulmonary will have subtherapeutic cefuroxime levels. This nomogram enables providers to determine when to administer additional antibiotics in patients receiving large additional volumes during cardiac surgeries. This rational approach to perioperative antibiotic dosing may result in a reduction in postoperative infection in this vulnerable patient population.
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