Background There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT. Methods Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized post-injury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n = 5) or recruitment maneuvers alone (control, n = 5) during ECMO. Results PaO 2 /FiO 2 after aspiration injury was 62.6 ± 8 mmHg and 60.9 ± 9.6 mmHg in the control and treatment group, respectively ( p = 0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls. Conclusions A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.

中文翻译：

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静脉-静脉 ECMO 作为评估严重 ARDS 动物模型肺灌洗和表面活性剂替代疗法的平台

背景 针对急性呼吸窘迫综合征 (ARDS) 潜在病理过程的治疗选择有限。实验性治疗策略针对在 ARDS 中变得紊乱的保护系统，例如表面活性剂。尽管表面活性剂替代疗法 (SRT) 在 ARDS 中的结果喜忧参半，但关于表面活性剂的时间和剂量策略的问题仍未得到完整解答。此外，文献中只有少数真正与临床相关的 ARDS 模型。我们研究的主要目的是创建一个临床相关、可重复的需要体外膜肺氧合 (ECMO) 的严重 ARDS 模型。其次，我们试图将该模型用作评估涉及盐水灌洗和 SRT 的支气管镜干预的平台。方法对约克夏猪进行气管切开并插管进行静脉-静脉ECMO支持，然后通过支气管镜检查使用胃液给予肺损伤。在 ECMO 期间，动物在受伤后随机接受支气管镜盐水灌洗联合 SRT 和复张操作（治疗，n = 5）或单独复张操作（对照，n = 5）。结果 对照组和治疗组吸入性损伤后PaO 2 /FiO 2 分别为62.6±8 mmHg和60.9±9.6 mmHg（p=0.95），满足重度ARDS的标准。ECMO 逆转了严重的低氧血症。在 ECMO 期间用盐水灌洗和 SRT 治疗后，治疗组和对照组之间的肺生理和血流动力学参数没有显着差异。结论建立了需要ECMO的临床相关重症ARDS猪模型。