Smith Jason E, Watts S, Spear A M, Wilson C, Kirkman E
CBR Division, Dstl Porton Down, Salisbury, UK.
Academic Department of Military Emergency Medicine, Royal Centre for Defence Medicine, Birmingham, UK.
J R Army Med Corps. 2019 Feb;165(1):51-56. doi: 10.1136/jramc-2018-001029. Epub 2018 Nov 12.
Primary blast lung injury causes intrapulmonary haemorrhage. A number of case reports have suggested the efficacy of recombinant activated factor VII (rFVIIa) in the treatment of diffuse alveolar haemorrhage from a range of medical causes, but its efficacy in blast lung is unknown. The aim of this study was to investigate whether nebulised rFVIIa attenuates the haemorrhagic effects of blast lung injury in an animal model.
Terminally anaesthetised rabbits subjected to blast lung injury were randomised to receive either rFVIIa or placebo via a nebuliser. The primary outcome was the level of blood iron-transferrin complex, a marker of the extent of blast lung injury, analysed using low temperature electron paramagnetic resonance spectroscopy.
Blast exposure led to a significant fall in iron-bound transferrin in both groups of animals (p<0.001), which remained depressed during the study. There were no significant differences in iron-transferrin between the rFVIIa and placebo treatment groups over the duration of the study (p=0.081), and there was no trend towards elevated iron-transferrin in the rFVIIa-treated group once drug treatment had started. There was suggestive evidence of systemic absorption of rFVIIa given via the inhaled route.
A single dose of nebulised rFVIIa did not attenuate pulmonary haemorrhage in a rabbit model of blast lung injury. As there was some evidence of systemic absorption, the inhaled route does not avoid the concern about potential thromboembolic complications from administration of rFVIIa.
原发性爆震性肺损伤可导致肺内出血。多项病例报告提示重组活化因子VII(rFVIIa)在治疗多种医学原因引起的弥漫性肺泡出血方面具有疗效,但其在爆震性肺损伤中的疗效尚不清楚。本研究的目的是调查雾化吸入rFVIIa是否能减轻动物模型中爆震性肺损伤的出血效应。
对接受爆震性肺损伤的终末期麻醉兔进行随机分组,通过雾化器分别给予rFVIIa或安慰剂。主要结局是血铁转铁蛋白复合物水平,这是爆震性肺损伤程度的一个指标,采用低温电子顺磁共振波谱分析。
两组动物爆震暴露后铁结合转铁蛋白均显著下降(p<0.001),且在研究期间一直处于较低水平。在研究期间,rFVIIa治疗组和安慰剂治疗组的铁转铁蛋白水平无显著差异(p=0.081),且rFVIIa治疗组在开始药物治疗后铁转铁蛋白也没有升高的趋势。有证据提示经吸入途径给予的rFVIIa存在全身吸收。
在兔爆震性肺损伤模型中,单剂量雾化吸入rFVIIa并不能减轻肺出血。由于有证据表明存在全身吸收,吸入途径并不能消除对rFVIIa给药潜在血栓栓塞并发症的担忧。