Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: Comparative effects of helium and nitrogen
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2005-05-01
Autores
Tonnellier, Marc
Ferrari, Fabio
Goldstein, Ivan
Sartorius, Alfonso
Marquette, Charles-Hugo
Rouby, Jean-Jacques
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Background: Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia. Methods: Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. Results: As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 ± 13 vs. 383 ± 84 μg/g in noninfected piglets and 10 ± 3 vs. 129 ± 108 μg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 ± 141 μg/g; P < 0.001) and no significant change in infected piglets (111 ± 104 μg/g). Conclusion: Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.
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ceftazidime, cephalosporin derivative, drug carrier, helium, nitrogen, oxygen, aerosol, animal experiment, animal model, animal tissue, artificial ventilation, bronchopneumonia, controlled study, drug administration route, drug delivery system, drug distribution, drug penetration, drug tissue level, experimental model, high performance liquid chromatography, nebulization, nonhuman, particle size, priority journal, Pseudomonas aeruginosa, swine, tissue distribution, ultrasound, Administration, Inhalation, Animals, Blood Gas Analysis, Bronchopneumonia, Ceftazidime, Cephalosporins, Escherichia coli Infections, Helium, Injections, Intravenous, Lung, Nebulizers and Vaporizers, Oxygen, Particle Size, Respiration, Artificial, Respiratory Mechanics, Swine, Ultrasonics
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Anesthesiology, v. 102, n. 5, p. 995-1000, 2005.