Effects of perfluorochemicals for intrapulmonary vancomycin administration and partial liquid ventilation in an animal model of meconium-injured lungs.

Mei-Jy Jeng, Yu-Sheng Lee, Wen-Jue Soong
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Abstract

Background: Acute lung injury, such as meconium aspiration syndrome in neonates, may present with exacerbated ventilation and perfusion abnormalities. This can impair the efficacy of intravenous antibiotic therapy in treating pulmonary infection. Intrapulmonary administration via perfluorochemical as a vehicle may adequately deliver drugs, such as the poorly pulmonary-penetrative antibiotic vancomycin, to affect lung regions while maintaining gas exchange and non-toxic serum level.

Methods: Twelve newborn piglets were injured with intra-tracheally installed human meconium, and randomly grouped into intravenous group (intravenous injection with vancomycin 15 mg/kg, followed by conventional gas ventilation) or intrapulmonary group (intrapulmonary instilled with vancomycin 15 mg/kg and perfluorochemical emulsion, followed by partial liquid ventilation). Blood samples were obtained to check vancomycin serum concentrations (0-240 mins). Lung tissues were tested for vancomycin contents.

Results: Intrapulmonary group animals had significantly lower vancomycin serum levels than the intravenous group, but vancomycin contents (198.9 +/- 72.5 microg/g dry tissue) in lung tissues was significantly higher than in the intravenous group (134.9 +/- 39.1 microg/g dry tissue) (p < 0.05). Gas exchange and lung compliance in the intrapulmonary group were also significantly better than in the intravenous group.

Conclusions: Perfluorochemical is a good vehicle to deliver vancomycin and maintains gas exchange in severe meconium-injured lungs.

全氟化学物质对肺内万古霉素给药和部分液体通气的影响
背景:急性肺损伤,如新生儿胎粪吸入综合征,可表现为加重的通气和灌注异常。这可能会损害静脉注射抗生素治疗肺部感染的疗效。通过全氟化学品作为载体的肺内给药可以充分输送药物,如肺渗透性差的抗生素万古霉素,以影响肺部区域,同时保持气体交换和无毒血清水平。方法:将12头经气管内放置人胎便损伤的新生仔猪随机分为静脉注射组(静脉注射万古霉素15 mg/kg,常规气体通气)和肺内注射组(肺内灌注万古霉素15 mg/kg,加全氟化学乳剂,部分液体通气)。取血检测万古霉素血清浓度(0 ~ 240 min)。检测肺组织万古霉素含量。结果:肺内组动物血清万古霉素水平显著低于静脉注射组,但肺组织万古霉素含量(198.9 +/- 72.5 μ g/g干组织)显著高于静脉注射组(134.9 +/- 39.1 μ g/g干组织)(p < 0.05)。肺内组的气体交换和肺顺应性也明显优于静脉注射组。结论:全氟化剂是一种良好的万古霉素输送载体,可维持严重胎粪损伤肺的气体交换。
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