Lung Collapse during Mini-Thoracotomy Reduces Penetration of Cefuroxime to the Tissue: Interstitial Microdialysis Study in Animal Models
Abstract
Background: Single-lung ventilation facilitates surgical exposure during minimally invasive cardiac surgery. However, a deeper knowledge of antibiotic distribution within a collapsed lung is mandatory for an effective antibiotic prophylaxis of pneumonia.
Patients and Methods: The pharmacokinetics/pharmacodynamics (PK/PD) of cefuroxime were compared between the plasma and interstitial fluid (ISF) of collapsed and ventilated lungs in ten anesthetized pigs, which were ventilated through a double-lumen endotracheal cannula. Cefuroxime (20 mg/kg) was administered in single 30-minutes intravenous infusion.
Samples of blood and lung microdialysate were collected until six hours post-dose. Ultrafiltration, in-vivo retrodialysis and high-performance liquid chromatography-tandem mass spectrometry were used to determine plasma and ISF concentrations of free drug.
The concentrations were examined with non-compartmental analysis and compartmental modeling. Results: The concentration of free cefuroxime in ISF was lower in the non-ventilated lung than the ventilated one, evidenced by a lung penetration factor of 47% vs. 63% (P ISF ventilated lung > plasma) could explain the absence of practically important differences in the time interval with the concentration of cefuroxime exceeding the MICs of sensitive strains (<= 4 mg/L).
Conclusion: The concentration of cefuroxime in the ISF of a collapsed porcine lung is lower than in a ventilated one; furthermore, its equilibration with plasma is delayed. Administration of the first cefuroxime dose earlier or at a higher rate may be warranted, as well as dose intensification of the perioperative prophylaxis of pneumonia caused by pathogens with higher MICs.