Lung Collapse during Mini-Thoracotomy Reduces Penetration of Cefuroxime to the Tissue: Interstitial Microdialysis Study in Animal Models.
Surg Infect (Larchmt)
; 22(3): 283-291, 2021 Apr.
Article
in En
| MEDLINE
| ID: mdl-32633629
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 necessary for effective antibiotic prophylaxis of pneumonia. Patients andMethods:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Atelectasis
/
Cefuroxime
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Surg Infect (Larchmt)
Journal subject:
BACTERIOLOGIA
Year:
2021
Type:
Article
Affiliation country:
Czech Republic