Enkhbaatar Perenlei, Cox Robert A, Traber Lillian D, Westphal Martin, Aimalohi Esechie, Morita Naoki, Prough Donald S, Herndon David N, Traber Daniel L
Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Crit Care Med. 2007 Dec;35(12):2805-10. doi: 10.1097/01.ccm.0000291647.18329.83.
Acute lung injury is a detrimental complication for victims of burn accidents. Airway obstruction plays an important role in pulmonary dysfunction in these patients. In this study, we tested the hypothesis that aerosolized anticoagulants will reduce the degree of airway obstruction and improve pulmonary function in sheep with severe combined burn and smoke inhalation injury by preventing the formation of airway fibrin clots.
Prospective, randomized, controlled, experimental animal study.
Investigational intensive care unit at a university hospital.
Adult female sheep.
After 7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40 degrees C) under halothane anesthesia. After injury, sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Sheep were randomly divided into five groups: sham, noninjured and nontreated (n = 6); control, injured and aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin, injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000 units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting at 2 hrs postinjury.
Cardiopulmonary hemodynamics were monitored during a 48-hr experimental time period. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and extensive airway obstruction. These variables were stable in sham animals. The aerosolization of rhAT or heparin alone did not significantly improve deteriorated pulmonary gas exchange. However, aerosolization of these anticoagulants in combination significantly attenuated all the observed pulmonary pathophysiology.
The results provide definitive evidence that aerosolized rhAT and heparin in combination may be a novel treatment strategy for pulmonary pathology in burn victims with smoke inhalation injury.
急性肺损伤是烧伤事故受害者的一种有害并发症。气道阻塞在这些患者的肺功能障碍中起重要作用。在本研究中，我们检验了这样一个假设，即雾化抗凝剂通过防止气道纤维蛋白凝块的形成，将减轻严重复合烧伤和烟雾吸入伤绵羊的气道阻塞程度并改善其肺功能。
前瞻性、随机、对照实验动物研究。
大学医院的研究重症监护病房。
成年雌性绵羊。
手术恢复7天后，绵羊接受皮肤烧伤（占全身表面积的40%，三度），并在氟烷麻醉下吸入棉烟（48次呼吸，<40摄氏度）。受伤后，绵羊被置于呼吸机上，并用乳酸林格氏液进行复苏。绵羊被随机分为五组：假手术组，未受伤且未治疗（n = 6）；对照组，受伤并用盐水雾化（n = 6）；重组人抗凝血酶（rhAT）+肝素组，受伤并用rhAT（每组290单位）和肝素（每组10,000单位）雾化（n = 6）；rhAT组，受伤并用rhAT单独雾化（每组290单位；n = 5）；肝素组，受伤并用肝素单独雾化（每组10,000单位；n = 5）。rhAT和肝素在受伤后2小时开始，每4小时雾化一次。
在48小时的实验时间段内监测心肺血流动力学。对照绵羊出现了多种急性肺损伤的体征。这种病理生理学包括肺气体交换和肺顺应性降低、肺水肿增加以及广泛的气道阻塞。这些变量在假手术动物中是稳定的。单独雾化rhAT或肝素并没有显著改善恶化的肺气体交换。然而，联合雾化这些抗凝剂显著减轻了所有观察到的肺部病理生理学变化。
结果提供了确凿的证据，表明联合雾化rhAT和肝素可能是烟雾吸入伤烧伤患者肺部病理的一种新的治疗策略。
