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Title: The effects of recombinant activated factor VII and hypotensive resuscitation on mortality and blood loss in a model of uncontrolled haemorrhage in the anaesthetised pig
Author: Sapsford, Wayne
ISNI:       0000 0001 3552 8970
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 2008
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Introduction: Haemorrhage is the leading cause of death from battlefield trauma and the second leading cause of death after civilian trauma. Blood loss causes 80% of all early trauma deaths. Control of non-compressible, truncal haemorrhage prior to surgical correction may save many lives especially in the case of military casualties where evacuation times to surgical care can be prolonged. A number of approaches have been advocated to limit blood loss. Several anecdotal reports suggest that recombinant activated factor VII (rFVlla) may arrest uncontrolled bleeding after trauma. However, the majority of prospective randomised controlled trials show little benefit in survival. The aim of this study was to determine whether rFVila could increase survival time and reduce the volume of blood loss in a model of noncompressible arterial haemorrhage over a prolonged prehospital phase, relevant to battlefield evacuation. A secondary aim was to determine the effects of hypotensive vs normotensive resuscitation on the efficacy of rFVlla. Methods: A prospective randomised controlled trial was conducted on 27 terminally anaesthetised pigs. The animals were randomly allocated to one of four treatment groups. All animals were subjected to a controlled haemorrhage of 40% of their estimated blood volume. They were then given either rFVlla (180 Jig/kg) or placebo (saline 0.3mUkg) intravenously and a 4-5 mm aortotomy created in the infra-renal aorta using a pre-implanted wire. Resuscitation was commenced with 0.9% saline to one of two target systolic arterial blood pressures: 110 mmHg (normotensive) or 80 mmHg (hypotensive). Results: Recombinant FVlIa was associated with a significantly prolonged survival time in animals managed hypotensively (214 [79-349] vs 35 [19-52] minutes mean [95% confidence interval], rFVlla vs placebo, p =0.03, Peto log rank test). There was no significant difference in survival time between those given rFVlla and placebo in groups managed normotensively (128 [6-250] vs 40 [15-66] minutes mean respectively, P =0.27). Both rFVlla and hypotensive management were associated with reduced volumes of uncontrolled haemorrhage. Post mortem evaluation revealed no evidence of inappropriate intravascular thrombi or microthrombi associated with the use of rFVlla. Conclusions: Recombinant FVlIa, combined with hypotensive resuscitation, can increase survival time and reduce blood loss in a model of uncontrolled arterial haemorrhage. The increase in survival time is clinically relevant for military evacuation of battlefield casualties to surgical care.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available