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Nebulised recombinant activated factor VII (rFVIIa) does not attenuate the haemorrhagic effects of blast lung injury
  1. Jason E Smith1,2,
  2. S Watts1,
  3. A M Spear1,
  4. C Wilson1 and
  5. E Kirkman1
  1. 1 CBR Division, Dstl Porton Down, Salisbury, UK
  2. 2 Academic Department of Military Emergency Medicine, Royal Centre for Defence Medicine, Birmingham, UK
  1. Correspondence to Jason E Smith, Academic Department of Military Emergency Medicine, Royal Centre for Defence Medicine, Birmingham B15 2TH, UK; jasonesmith{at}nhs.net

Abstract

Introduction 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.

Methods 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.

Results 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.

Conclusion 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.

  • trauma management
  • biophysics
  • physiology

This material is licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gsi.gov.uk.

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Footnotes

  • Contributors The study was conceived by SW, EK and JES. All authors were involved in carrying out aspects of the study. Data analysis and interpretation were undertaken by EK, SW and JES. The initial draft was written by JES, and subsequent revisions were made by EK and SW. All authors have contributed to and approved the final manuscript for publication.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Disclaimer The contents include material subject to © Crown copyright (YYY), Dstl. This material is licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gsi.gov.uk.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The study was ethically reviewed and conducted in accordance with the Animals (Scientific Procedures) Act, 1986.

  • Provenance and peer review Commissioned; internally peer reviewed.

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