Editorial Views  |   August 2019
Nebulized Antibiotics: Epithelial Lining Fluid Concentrations Overestimate Lung Tissue Concentrations
Author Notes
  • From the Sorbonne University of Paris, Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
  • This editorial accompanies the article on p. 344.
    This editorial accompanies the article on p. 344.×
  • Accepted for publication May 1, 2019.
    Accepted for publication May 1, 2019.×
  • Address correspondence to Dr. Rouby: jjrouby@invivo.edu
Article Information
Editorial Views / Respiratory System
Editorial Views   |   August 2019
Nebulized Antibiotics: Epithelial Lining Fluid Concentrations Overestimate Lung Tissue Concentrations
Anesthesiology 8 2019, Vol.131, 229-232. doi:10.1097/ALN.0000000000002824
Anesthesiology 8 2019, Vol.131, 229-232. doi:10.1097/ALN.0000000000002824
In this issue of Anesthesiology, Dhanani et al.1  provide evidence that the tobramycin lung interstitial space fluid concentrations measured after a single 400-mg aerosol dose are twice those measured after the equivalent intravenous dose. Tobramycin interstitial space fluid concentrations were measured using samples obtained by microdialysis catheters surgically inserted in anesthetized and mechanically ventilated ewes with normal lungs. The study confirms the results of a number of previous experiments that demonstrated high antibiotic lung tissue concentrations after nebulization compared with the intravenous route.2  In these studies, the antibiotic lung tissue concentrations were measured using high-performance liquid chromatography performed on postmortem tissue samples after they were cryomixed in nitrogen, weighed, and homogenized in buffer solution.3  Despite of some limitations—a small number of animals, the lack of optimization of the nebulization procedure, the inclusion of animals with normal lungs—the study is of great interest because it assesses concomitantly tobramycin lung concentrations by two independent methods: microdialysis for measuring lung interstitial space fluid concentrations and bronchoalveolar lavage for measuring epithelial lining fluid concentrations.4  The former is the reference method, but it cannot be used routinely in clinical practice because of its invasiveness. The latter, despite numerous methodologic issues, is widely used in clinical practice to assess pharmacokinetic profiles after antibiotic nebulization.5–7  As expected, epithelial lining fluid and lung interstitial space fluid concentrations were much higher after tobramycin nebulization than after intravenous administration. However, the 100-fold overestimation of lung interstitial space fluid concentrations by epithelial lining fluid concentrations was not anticipated and appears to be a result of primary importance with a direct clinical relevance.