观察性研究：机械通气绵羊模型中雾化与静脉给予放射性标记妥布霉素的肺部分布比较。

Comparative lung distribution of radiolabeled tobramycin between nebulized and intravenous administration in a mechanically-ventilated ovine model, an observational study.

机构信息

UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, Australia; Critical Care Research Group, The University of Queensland, Brisbane, Australia.

Department of Nuclear Medicine and Specialised PET Services Queensland, The Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.

出版信息

Int J Antimicrob Agents. 2021 Feb;57(2):106232. doi: 10.1016/j.ijantimicag.2020.106232. Epub 2020 Nov 21.

DOI:10.1016/j.ijantimicag.2020.106232

PMID:33232733

Abstract

BACKGROUND

Ventilator-associated pneumonia is common and is treated using nebulized antibiotics. Although adequate pulmonary biodistribution is important for antibiotic effect, there is a lack of data for both intravenous (IV) and nebulized antibiotic administration during mechanical ventilation.

OBJECTIVE

To describe the comparative pulmonary regional distribution of IV and nebulized technetium-99m-labeled tobramycin (Tc-tobramycin) 400 mg in a mechanically-ventilated ovine model.

METHODS

The study was performed in a mechanically-ventilated ovine model. Tc-tobramycin 400 mg was obtained using a radiolabeling process. Computed tomography (CT) was performed. Ten sheep were given Tc-tobramycin 400 mg via either an IV (five sheep) or nebulized (five sheep) route. Planar images (dorsal, ventral, left lateral and right lateral) were obtained using a gamma camera. Blood samples were obtained every 15 min for 1 h (4 time points) and lung, liver, both kidney, and urine samples were obtained post-mortem.

RESULTS

Ten sheep were anesthetized and mechanically ventilated. Whole-lung deposition of nebulized Tc-tobramycin 400 mg was significantly lower than with IV (8.8% vs. 57.1%, P<0.001). For both administration routes, there was significantly lower deposition in upper lung zones compared with the rest of the lungs. Dorsal deposition was significantly higher with nebulized Tc-tobramycin 400 mg compared with IV (68.9% vs. 58.9%, P=0.003). Lung concentrations of Tc-tobramycin were higher with IV compared with nebulized administration. There were significantly higher concentrations of Tc-tobramycin in blood, liver and urine with IV administration compared with nebulized.

CONCLUSIONS

Nebulization resulted in lower whole and regional lung deposition of Tc-tobramycin compared with IV administration and appeared to be associated with low blood and extra-pulmonary organ concentrations.

摘要

背景

呼吸机相关性肺炎很常见，通常使用雾化抗生素进行治疗。尽管抗生素在肺部的充分分布对于疗效很重要，但在机械通气期间，静脉内（IV）和雾化抗生素给药均缺乏相关数据。

目的

描述在机械通气绵羊模型中，静脉内和雾化给予 99m 锝标记妥布霉素（Tc-妥布霉素）400mg 的比较肺区域性分布。

方法

该研究在机械通气绵羊模型中进行。Tc-妥布霉素 400mg 通过放射性标记过程获得。进行计算机断层扫描（CT）。10 只绵羊通过静脉内（5 只绵羊）或雾化（5 只绵羊）途径给予 Tc-妥布霉素 400mg。使用伽马相机获得平面图像（背侧、腹侧、左侧和右侧）。在 1 小时（4 个时间点）内每 15 分钟采集一次血样，并在死后采集肺、肝、双侧肾脏和尿液样本。

结果

10 只绵羊被麻醉并进行机械通气。与 IV 途径相比，雾化 Tc-妥布霉素 400mg 的全肺沉积明显较低（8.8% vs. 57.1%，P<0.001）。对于两种给药途径，与其余肺部相比，上肺区的沉积明显较低。与 IV 途径相比，雾化 Tc-妥布霉素 400mg 的背侧沉积明显较高（68.9% vs. 58.9%，P=0.003）。与雾化给药相比，IV 途径的肺组织 Tc-妥布霉素浓度较高。与雾化给药相比，IV 给药时血液、肝脏和尿液中的 Tc-妥布霉素浓度明显较高。