Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury.
Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury.
复制标题
DOI：
10.1097/shk.0b013e31827b47bb
复制
发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Nieman G
中科院分区：
文献类型：
--
作者：
Roy S;Habashi N;Sadowitz B;Andrews P;Ge L;Wang G;Roy P;Ghosh A;Kuhn M;Satalin J;Gatto LA;Lin X;Dean DA;Vodovotz Y;Nieman G
尽管目前的护理标准——低潮气量（LTV）通气被广泛使用，但急性呼吸窘迫综合征（ARDS）每年仍折磨着20万患者，死亡率为30%至60%。高通透性肺泡水肿和不稳定发生在ARDS发展的早期，在肺损伤的临床症状出现之前，是潜在的治疗目标。我们假设早期应用保护性通气策略（气道压力释放通气[APRV]）可以稳定肺泡，减少肺泡水肿，防止ARDS的发展。约克郡猪（30-40 kg）被麻醉，并进行两次打击损伤：(a)肠缺血再灌注，(b)腹膜败血症，或假手术。手术后，根据目前公布的APRV指南，将猪随机分为APRV组（n= 4）；LTV通气（n= 3），使用当前发布的ARDS网络指南（6 mL/kg）；或sham （n= 5）。所有猪的临床护理均按照幸存败血症运动指南进行。处死动物，48 h尸检。测量动脉血气以评估临床肺损伤的发展。测定肺组织上皮钙粘蛋白（E-cadherin）以评估肺泡通透性。测定支气管肺泡灌洗液（BALF）表面活性剂蛋白A以评估肺泡稳定性。48 h时分析肺水肿含量和组织病理学。气道压力释放通气猪未发生ARDS。相比之下，LTV通气组猪符合ARDS标准（PaO 2/FIO 2比值）（APRV：基线= 471±16,48 h= 392±8；与LTV通气组相比，基线= 551±28,48 h= 138±88，P< 0.001）。与LTV通气相比，气道压力释放通气能保持肺泡上皮的完整性，肺组织中E-cadherin水平升高（P< 0.05）。表面活性剂蛋白A水平在APRV组的BALF中较高，提示APRV保持了肺泡的稳定性。定量组织学评分显示，与LTV通气相比，APRV组ARDS的所有柱头均有改善（P< 0.05）。气道压力释放通气组肺水肿（干湿重）明显低于LTV通气组（P< 0.05）。在受伤后立即使用APRV进行保护性通气可防止ARDS的发生。肺水肿的减少、肺e -钙粘蛋白的保留和BALF中表面活性剂蛋白A的丰度表明，APRV减轻了肺通透性、水肿和表面活性剂的降解。保护性通气可以改变临床模式，从支持治疗ARDS合并LTV通气转变为预防ARDS合并APRV的发展。*纽约州锡拉丘兹上州医科大学外科心肺和重症监护实验室；†多创伤科，R. Adams Cowley休克创伤中心，马里兰州巴尔的摩；芝加哥大学，芝加哥，伊利诺伊州；§哥伦比亚大学营养学系，纽约；∥SUNY Cortland生物系，Cortland；¶纽约州罗彻斯特市罗彻斯特大学医学中心新生儿科；和**外科，匹兹堡大学，匹兹堡，宾夕法尼亚州
Acute respiratory distress syndrome (ARDS) afflicts 200,000 patients annually with a mortality rate of 30% to 60% despite wide use of low tidal volume (LTV) ventilation, the present standard of care. High-permeability alveolar edema and instability occur early in the development of ARDS, before clinical signs of lung injury, and represent potential targets for therapy. We hypothesize that early application of a protective ventilation strategy (airway pressure release ventilation [APRV]) will stabilize alveoli and reduce alveolar edema, preventing the development of ARDS. Yorkshire pigs (30–40 kg) were anesthetized and subjected to two-hit injury:(a) intestinal ischemia-reperfusion,(b) peritoneal sepsis, or sham surgery. Following surgery, pigs were randomized into APRV (n= 4), according to current published guidelines for APRV; LTV ventilation (n= 3), using the current published ARDS Network guidelines (6 mL/kg); or sham (n= 5). The clinical care of all pigs was administered per the Surviving Sepsis Campaign guidelines. Animals were killed, and necropsy performed at 48 h. Arterial blood gases were measured to assess for the development of clinical lung injury. Lung tissue epithelial cadherin (E-cadherin) was measured to assess alveolar permeability. Bronchoalveolar lavage fluid (BALF) surfactant protein A was measured to assess alveolar stability. Lung edema content and histopathology were analyzed at 48 h. Airway pressure release ventilation pigs did not develop ARDS. In contrast, pigs in the LTV ventilation met ARDS criteria (PaO 2/FIO 2 ratio)(APRV: baseline= 471±16; 48 h= 392±8; vs. LTV ventilation: baseline= 551±28; 48 h= 138±88; P< 0.001). Airway pressure release ventilation preserved alveolar epithelial integrity demonstrated by higher levels of E-cadherin in lung tissue as compared with LTV ventilation (P< 0.05). Surfactant protein A levels were higher in BALF from the APRV group, suggesting APRV preserved alveolar stability. Quantitative histologic scoring showed improvements in all stigmata of ARDS in the APRV group versus the LTV ventilation (P< 0.05). Airway pressure release ventilation had significantly lower lung edema (wet-dry weight) than LTV ventilation (P< 0.05). Protective ventilation with APRV immediately following injury prevents development of ARDS. Reduction in lung edema, preservation of lung E-cadherin, and surfactant protein A abundance in BALF suggest that APRV attenuates lung permeability, edema, and surfactant degradation. Protective ventilation could change the clinical paradigm from supportive care for ARDS with LTV ventilation to preventing development of ARDS with APRV.* Cardiopulmonary and Critical Care Laboratory, Department of Surgery, Upstate Medical University, Syracuse, New York;† Multitrauma Unit, R. Adams Cowley Shock Trauma Center, Baltimore, Maryland;‡ University of Chicago, Chicago, Illinois; § Department of Nutrition, Columbia University, New York;∥ Department of Biology, SUNY Cortland, Cortland;¶ Department of Pediatrics, Neonatology University of Rochester Medical Center, Rochester, New York; and** Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania