Background: Single-lung ventilation facilitates surgical exposure during minimally invasive cardiac surgery. However, a deeper knowledge of antibiotic distribution within a collapsed lung is necessary for 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 10 anesthetized pigs, which were ventilated through a double-lumen endotracheal cannula. Cefuroxime (20 mg/kg) was administered in single 30-minute 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% versus 63% (p < 0.05), the ratio between maximum concentrations (65%, p < 0.05), and the ratio between the areas under the concentration-time curve (78%, p = 0.12). The time needed to reach a minimum inhibitory concentration (MIC) was 30%-40% longer for a collapsed lung than for a ventilated one. In addition, a delay of 10-40 minutes was observed for lung ISF compared with plasma. The mean residence time values (ISF collapsed lung > 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.

Animal Research Facility Faculty of Military Health Sciences University of Defense Třebešská Králové Czech Republic

Department of Anesthesiology Resuscitation and Intensive Medicine Charles University Faculty of Medicine University Hospital Hradec Králové Hradec Králové Czech Republic

Department of Cardiac Surgery Resuscitation and Intensive Medicine Charles University Faculty of Medicine University Hospital Hradec Králové Hradec Králové Czech Republic

Department of Pharmacology Resuscitation and Intensive Medicine Charles University Faculty of Medicine University Hospital Hradec Králové Hradec Králové Czech Republic

Institute of Clinical Biochemistry and Diagnoses Resuscitation and Intensive Medicine Charles University Faculty of Medicine University Hospital Hradec Králové Hradec Králové Czech Republic

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