Lung tissue concentrations of nebulized amikacin during mechanical ventilation in piglets with healthy lungs
Lung tissue concentrations of nebulized amikacin during mechanical ventilation in piglets with healthy lungs
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DOI：
10.1164/ajrccm.165.2.2107025
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发表时间：
2002-01-15
影响因子：
24.7
通讯作者：
Rouby, JJ
中科院分区：
文献类型：
--
作者：
Goldstein, I;Wallet, F;Rouby, JJ
肺实质中氨基糖苷类的组织浓度是杀菌效率的主要决定因素。本研究的目的是比较机械通气期间通过超声雾化器或静脉输注给予阿米卡星的肺沉积。18头健康的通气仔猪通过静脉输注接受单次每日剂量的阿米卡星（15 mg . kg（-1））和18个气雾剂（12 ml中1 g）。到达气管支气管树的雾化阿米卡星的量代表初始剂量的40 +/-5%，空气动力学尺寸分布显示50%的颗粒的质量中值直径在0.5和5 μ m之间。在第二次给药后的不同时间间隔处死动物。用免疫酶法测定了冷冻混合的多个肺标本中阿米卡星的组织浓度。雾化阿米卡星的肺浓度，峰值为208 +/- 76 μ g。g（-1），比静脉注射阿米卡星的肺浓度高10倍以上，并均匀分布于整个肺实质。阿米卡星血浆浓度低于5 mmol。在雾化后6小时后测量L（-1）。总之，超声雾化阿米卡星导致高组织浓度，远高于大多数革兰氏阴性菌株的最低抑菌浓度。
The tissue concentration of aminoglycosides in lung parenchyma is the main determinant of bactericidal efficiency. The aim of the study was to compare the lung deposition of amikacin administered either by an ultrasonic nebulizer or by intravenous infusion during mechanical ventilation. Eighteen healthy ventilated piglets received a single daily dose of amikacin by intravenous infusion (15 mg . kg(-1)) and 18 by aerosol (1 g in 12 ml). The amount of aerosolized amikacin reaching the tracheobronchial tree represented 40 +/- 5% of the initial dose with an aerodynamic size distribution showing 50% of particles ranging between 0.5 and 5 mum mass median diameter. Animals were killed at different time intervals after the second dose. Tissue concentrations of amikacin were determined on cryomixed multiple lung specimen by an immunoenzymatic method. The lung concentrations of nebulized amikacin, peaking at 208 +/- 76 mug . g(-1), were more than 10-fold higher than the lung concentrations of intravenous amikacin and were homogeneously distributed throughout the lung parenchyma. Amikacin plasma concentrations lower than 5 mmol . l(-1) were measured after the sixth hour after the nebulization. In conclusion, the ultrasonic nebulization of amikacin resulted in high tissue concentrations, far above the minimal inhibitory concentrations of most gram-negative strains.