Influence of lung aeration on pulmonary concentrations of nebulized and intravenous amikacin in ventilated piglets with severe bronchopneumonia
Influence of lung aeration on pulmonary concentrations of nebulized and intravenous amikacin in ventilated piglets with severe bronchopneumonia
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DOI：
10.1097/00000542-200207000-00028
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发表时间：
2002-07-01
期刊：
影响因子：
8.8
通讯作者：
Rouby, JJ
中科院分区：
文献类型：
--
作者：
Elman, M;Goldstein, I;Rouby, JJ
背景：在感染的肺实质中静脉给药的氨基糖苷类药物的肺浓度通常很低。雾化吸入是增加肺浓度的一种替代方法，尽管化脓性塞子阻塞细支气管会减少肺通气量，从而损害肺沉积。方法：将10(6)cfu/ml的大肠杆菌悬液接种于麻醉仔猪的下肺，建立实验性支气管肺炎模型。机械通气24 h后，7只动物静脉注射阿米卡星15 mg/kg，11只动物雾化吸入阿米卡星40 mg/kg，间隔24 h。结果：雾化吸入阿米卡星15 mg/kg后，38%可达气管支气管树。雾化吸入后，阿米卡星肺内浓度始终高于静脉给药后，随着实质感染的扩大而降低，并受肺充气的显著影响：局灶性支气管炎的肺段为197±/-165mUg/g(P=0.03)，汇合性支气管炎的肺段为40+/-62mg/g(P=0.001)，肺段为18+/-7mg/g，肺通气量为30%以下的肺段为7+/-4mug/g。肺通气量50%或以上的肺段分别为65+/-9和2+/-3mug/g。结论：在猪重症支气管炎模型中，雾化吸入丁胺卡那星的肺内药物浓度是静脉给药的3-30倍。肺通气量越大，感染肺段的阿米卡星肺浓度越高。
Background: Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration.Methods: An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 10(6) cfu/ml Escherichia coli. After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals. One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections.Results: Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree. Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 mug/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 mug/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 mug/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 mug/g in lung segments with lung aeration of 50% or more.Conclusions: In a porcine model of severe bronchopneumonia, the nebulization of amikacin provided 3-30 times higher pulmonary concentrations than the intravenous administration of an equivalent dose. The greater the lung aeration, the higher were the amikacin pulmonary concentrations found in the infected lung segments.