Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

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.