Sapsford Wayne, Watts Sarah, Cooper Graham, Kirkman Emrys
Department of Biomedical ciences, Dstl Porton Down, Salisbury, UK.
J Trauma. 2007 Apr;62(4):868-79. doi: 10.1097/ta.0b013e318034204b.
Hemorrhage is the leading cause of death in battlefield casualties and the second leading cause of death after civilian trauma. Evacuation time for military casualties to surgical care can be prolonged and improved hemostasis could greatly reduce mortality. There are several anecdotal reports that recombinant activated factor VII (rFVIIa) may arrest uncontrolled bleeding after trauma. However, the majority of prospective randomized controlled trials show little benefit in survival. The aim of this study was to determine whether rFVIIa could increase survival time within a clinically relevant time scale for military practice and reduce the volume of blood loss in a model of incompressible arterial hemorrhage. A secondary aim was to determine the effects of hypotensive versus normotensive resuscitation on the effectiveness of rFVIIa.
Terminally anaesthetized Large White pigs were randomly allocated to one of four treatment groups. All animals received a controlled hemorrhage of 40% of the total estimated blood volume. They were given either rFVIIa (180 microg/kg) or placebo (saline 0.3 mL/kg) intravenously and a 4 to 5 mm longitudinal aortotomy created in the infra renal aorta before resuscitation commenced with 0.9% saline to one of two target systolic arterial blood pressures (SBPs): 110 mm Hg (normotensive) or 80 mm Hg (hypotensive). Group sizes were as follows: placebo/normotensive (6), placebo/hypotensive (7), rFVIIa/normotensive (7), and rFVIIa/hypotensive (7). Survival was monitored for a maximum of 6 hours after the onset of resuscitation.
rFVIIa was associated with a significantly prolonged survival time in animals managed hypotensively (214 [79-349] vs. 35 [19-52] minutes mean [95% confidence interval] rFVIIa vs. placebo, p = 0.03 Peto log rank test). There was no significant difference in survival time between those given rFVIIa and placebo in groups managed normotensively (128 [6-249] vs. 40 [15-66] minutes respectively, p = 0.27). Both rFVIIa and hypotensive management were associated with reduced uncontrolled hemorrhage volumes. There was no evidence of inappropriate intravascular thrombi or microthrombi associated with the use of rFVIIa.
rFVIIa, combined with hypotensive resuscitation, can increase survival time and reduce hemorrhage in a model of arterial hemorrhage. The increase in survival time is clinically relevant for military evacuation of battlefield casualties to surgical care.
出血是战场伤员死亡的首要原因，也是平民创伤后死亡的第二大原因。军事伤员接受手术治疗的转运时间可能会延长，改善止血可大大降低死亡率。有几篇轶事报道称重组活化因子VII（rFVIIa）可能会止住创伤后的失控性出血。然而，大多数前瞻性随机对照试验显示对生存率几乎没有益处。本研究的目的是确定rFVIIa在军事实践的临床相关时间范围内是否能增加生存时间，并减少不可压缩性动脉出血模型中的失血量。次要目的是确定低血压复苏与正常血压复苏对rFVIIa有效性的影响。
将终末期麻醉的大白猪随机分配到四个治疗组之一。所有动物均接受控制性出血，出血量为估计总血容量的40%。在开始用0.9%生理盐水进行复苏前，它们被静脉注射rFVIIa（180微克/千克）或安慰剂（生理盐水0.3毫升/千克），并在肾下主动脉处做一个4至5毫米长的纵向主动脉切开术，以达到两个目标收缩期动脉血压（SBP）之一：110毫米汞柱（正常血压）或80毫米汞柱（低血压）。每组的动物数量如下：安慰剂/正常血压组（6只）、安慰剂/低血压组（7只）、rFVIIa/正常血压组（7只）和rFVIIa/低血压组（7只）。复苏开始后最多监测6小时的生存情况。
在低血压处理的动物中，rFVIIa与显著延长的生存时间相关（平均生存时间[95%置信区间]：rFVIIa组为214[79 - 349]分钟，安慰剂组为35[19 - 52]分钟，Peto对数秩检验，p = 0.03）。在正常血压处理的组中，给予rFVIIa和安慰剂的动物生存时间无显著差异（分别为128[6 - 249]分钟和40[15 - 66]分钟，p = 0.27）。rFVIIa和低血压处理均与减少失控性出血量相关。没有证据表明使用rFVIIa会导致不适当的血管内血栓或微血栓形成。
rFVIIa与低血压复苏相结合，可增加动脉出血模型中的生存时间并减少出血。生存时间延长对战场伤员转运至外科治疗具有临床意义。
