TREATMENT OF ACUTE HYPOXEMIC RESPIRATORY FAILURE

各种原因的急性肺损伤患者弥漫性肺泡 损伤会导致肺水肿和急性缺氧性呼吸衰竭。 因为没有针对原发肺损伤的特效预防或治疗 可用的支持性治疗包括正压通气 呼气末压力(PEEP)和吸入氧气水平较高 分数(FI02)，心输出量(QT)与血浆容量维持 扩张。该方法的一个不良结果是非缺氧性患者。 限制在呼吸机上等待自发的有界循环 危重病并发症时肺水肿的清除 发展。可以想象，早期积极的心血管管理可以 减少血管外肺液(EVLL)而不降低QT、动脉 氧转运(QO2)和组织氧利用(VO2)。这 应用程序描述了评估这一方法的四个方面的建议。 1)在酸吸入和肺挫伤模型上，肺楔形 通过血浆置换，压力(PPW)将从10托降低到5托 确定对EVLL和血管活性药物(硝普钠或 多巴胺)，以确定QT、QO2和VO2是否可以 维持在低PPW，对肺气体交换无不良影响。2) 血浆置换降低QT对所需QO2临界值的影响 维持有氧代谢的研究将在急性肺损伤前后进行 静脉注射油酸诱导犬损伤，并在 使用PEEP或血管活性药物治疗。3)星际关系 犬油酸性肺水肿时左室受压， 这种功能障碍可被硝普钠纠正。以确定这些是否 作用是由于急性肺损伤，直接作用于油酸 对心肌的影响，或改变后负荷的影响，我们将 将它们与Starling关系的相应影响进行比较 左房注射油酸后的等容收缩功能 不会造成肺损伤。这些结果将证明这一点是否 心血管管理有效减少不同犬模型的EVLL 急性肺损伤的风险，以及潜在风险对管理的影响 心血管抑制与有氧极限的潜在变化 新陈代谢。4)然后我们将测试血浆置换(以降低PPW)和 多巴胺(维持心输出量)可减少EVLL和持续时间 急性低氧血症患者重症监护的并发症 呼吸衰竭。

In patients with acute lung injury of diverse etiologies, diffuse alveolar damage leads to pulmonary edema and acute hypoxemic respiratory failure. Because no specific prevention or treatment of the primary lung injury is available, supportive therapy consists of positive pressure ventilation with high levels of end-expiratory pressure (Peep) and inspired oxygen fraction (FI02) while cardiac output (Qt) is maintined with plasma volume expansion. One adverse outcome of the approach is a non-hypoxic patient with bounding circulation confined to a ventilator awaiting spontaneous clearance of the lung edema while complications of critical illness develop. Conceivably, early aggressive cardiovascular management can reduce extravascular lung liquid (EVLL) without reducing Qt, arterial oxygen transport (QO2) and tissue oxygen utilitization (VO2). This application describes four proposals to evaluate aspects of this approach. 1) In canine models of acid aspiration and lung contusion, pulmonary wedge pressure (Ppw) will be reduced from 10 to 5 torr by plasmapheresis to determine the effect on EVLL, and vasoactive drugs (nitroprusside or dopamine) will be infused to determine whether Qt, QO2, and VO2 can be maintained at low Ppw without adverse effects on lung gas exchange. 2) The effect of reducing Qt by plasmapheresis on the critical value of QO2 needed to maintain aerobic metabolism will be studied before and after acute lung injury is induced in dogs by intravenous oleic acid and again during treatment with Peep or vasoactive drugs. 3) The Starling relationship of the left ventricle is depressed in canine oleic acid pulmonary edema, and this dysfunction is corrected by nitroprusside. To determine whether these effects are due to the acute lung injury, to direct effects of oleic acid on the myocardium, or to effects of altered resistive afterload, we will compare them with corresponding effects on Starling relationships and on isovolemic contractility after left atrial injection of oleic acid which does not cause lung damage. These results will demonstrate whether this cardiovascular management effectively reduces EVLL in diverse canine models of acute lung injury, and how the management is affected by potential cardiovascular depression and by potential changes in the limits of aerobic metabolism. 4) Then we will test whether plasmapheresis (to lower Ppw) and dopamine (to maintain cardiac output) reduce EVLL and the duration and complications of intensive care in patients with acute hypoxemic respiratory failure.