Williams Timothy K, Neff Lucas P, Johnson Michael Austin, Russo Rachel M, Ferencz Sarah-Ashley, Davidson Anders J, Clement Nathan F, Grayson John Kevin, Rasmussen Todd E
From the Clinical Investigation Facility (T.K.W., L.P.N., N.F.C., J.K.G.) and Heart, Lung and Vascular Center (T.K.W.), David Grant USAF Medical Center, Travis Air Force Base, California; Departments of Emergency Medicine (M.A.J.) and Surgery (R.M.R., A.J.D.), UC Davis Medical Center, Sacramento, California; Department of Surgery (S.-A.F.), Wright State University, Dayton, Ohio; and US Combat Casualty Care Research Program (T.E.R.), US Army Medical Research and Materiel Command, Fort Detrick, Maryland.
J Trauma Acute Care Surg. 2017 Apr;82(4):694-703. doi: 10.1097/TA.0000000000001372.
Future endovascular hemorrhage control devices will require features that mitigate the adverse effects of vessel occlusion. Permissive regional hypoperfusion (PRH) with variable aortic control (VAC) is a novel strategy to minimize hemorrhage and reduce the ischemic burden of complete aortic occlusion (AO). The objective of this study was to compare PRH with VAC to AO in a lethal model of hemorrhage.
Twenty-five swine underwent cannulation of the supraceliac aorta, with diversion of aortic flow through an automated extracorporeal circuit. After creation of uncontrolled liver hemorrhage, animals were randomized to 90 minutes of treatment: Control (full, unregulated flow; n = 5), AO (no flow; n = 10), and PRH with VAC (dynamic distal flow initiated after 20 minutes of AO; n = 10). In the PRH group, distal flow rates were regulated between 100 and 300 mL/min based on a desired, preset range of proximal mean arterial pressure (MAP). At 90 minutes, damage control surgery, resuscitation, and restoration of full flow ensued. Critical care continued for 4.5 hours or until death. Hemodynamic parameters and markers of ischemia were recorded.
Study survival was 0%, 50%, and 90% for control, AO, and VAC, respectively (p < 0.01). During intervention, VAC resulted in more physiologic proximal MAP (84 ± 18 mm Hg vs. 105 ± 9 mm Hg, p < 0.01) and higher renal blood flow than AO animals (p = 0.02). During critical care, VAC resulted in higher proximal MAP (73 ± 8 mm Hg vs. 50 ± 6 mm Hg, p < 0.01), carotid and renal blood flow (p < 0.01), lactate clearance (p < 0.01), and urine output (p < 0.01) than AO despite requiring half the volume of crystalloids to maintain proximal MAP ≥50 mm Hg (p < 0.01).
Permissive regional hypoperfusion with variable aortic control minimizes the adverse effects of distal ischemia, optimizes proximal pressure to the brain and heart, and prevents exsanguination in this model of lethal hemorrhage. These findings provide foundational knowledge for the continued development of this novel paradigm and inform next-generation endovascular designs.
未来的血管内出血控制装置将需要具备减轻血管闭塞不良反应的特性。允许性区域低灌注（PRH）联合可变主动脉控制（VAC）是一种将出血降至最低并减轻完全主动脉闭塞（AO）缺血负担的新策略。本研究的目的是在致死性出血模型中比较PRH联合VAC与AO的效果。
25头猪接受了腹腔干上方主动脉插管，通过自动体外循环分流主动脉血流。在造成无法控制的肝脏出血后，将动物随机分为90分钟的治疗组：对照组（全流量、无调节；n = 5）、AO组（无血流；n = 10）和PRH联合VAC组（AO 20分钟后启动动态远端血流；n = 10）。在PRH组中，根据预设的近端平均动脉压（MAP）目标范围，将远端血流速率调节在100至300 mL/分钟之间。90分钟后，进行损伤控制手术、复苏并恢复全流量。重症监护持续4.5小时或直至死亡。记录血流动力学参数和缺血标志物。
对照组、AO组和VAC组的研究生存率分别为0%、50%和90%（p < 0.01）。在干预期间，VAC组的近端MAP更接近生理水平（84 ± 18 mmHg对105 ± 9 mmHg，p < 0.01），且肾血流量高于AO组动物（p = 0.02）。在重症监护期间，尽管维持近端MAP≥50 mmHg所需的晶体液量仅为AO组的一半（p < 0.01），但VAC组的近端MAP（73 ± 8 mmHg对50 ± 6 mmHg，p < 0.01）、颈动脉和肾血流量（p < 0.01）、乳酸清除率（p < 0.01）和尿量（p < 0.01）均高于AO组。
允许性区域低灌注联合可变主动脉控制可将远端缺血的不良反应降至最低，优化大脑和心脏的近端压力，并在该致死性出血模型中防止失血过多。这些发现为这一新范式的持续发展提供了基础知识，并为下一代血管内设计提供了参考。
