Inhaled recombinant activated factor VII (rFVIIa) in the management of blast lung injury

Abstract

Injuries caused by explosions are an increasing threat. Primary blast lung injury, caused by the blast wave, precipitates intrapulmonary haemorrhage and subsequent oedema and inflammation. Treatment options are currently limited to supportive measures including mechanical ventilation. Recombinant activated factor VII (rFVIIa) promotes coagulation and reduces bleeding. It has been used to manage patients with traumatic bleeding that is not amenable to surgical haemorrhage control. Retrospective database analyses were undertaken to establish the epidemiology of blast lung injury in the military patient population, and the use of rFVIIa within military hospitals. These showed that the incidence of blast lung injury in those injured by explosion in the most recent conflict in Afghanistan is 11%. Use of intravenous rFVIIa in military hospitals is declining, due to a combination of factors including the introduction of bespoke targeted resuscitation, although rFVIIa may still have a role in the management of patients with haemorrhage not amenable to conventional treatments, such as blast lung injury. A programme of work was undertaken to develop an animal model of blast lung injury, in which a trial of nebulised rFVIIa could be undertaken. This involved the development of a reliable and reproducible model of blast lung injury in the rabbit, involving a shock tube. Work was also undertaken to establish that rFVIIa remained active after nebulisation, to define the distribution in the lungs following nebulisation, and to determine the amount deposited following nebulisation. Results showed that rFVIIa remains active following nebulisation, is widely distributed, and 10-15% is deposited in the lungs. The clinical problem of blast lung injury has therefore been defined in the population of interest, and the experimental work has established the methodology enabling a proof of principle study to be undertaken to determine whether rFVIIa, delivered by nebulisation, attenuates the haemorrhagic phase of blast lung injury.