Qaqish Robert, Watanabe Yui, Galasso Marcos, Summers Cara, Ali A Adil, Takahashi Mamoru, Gazzalle Anajara, Liu Mingyao, Keshavjee Shaf, Cypel Marcelo, Del Sorbo Lorenzo
Latner Thoracic Surgery Research Laboratories, Toronto, Canada.
University of Toronto, Toronto, ON, Canada.
Intensive Care Med Exp. 2020 Oct 27;8(1):63. doi: 10.1186/s40635-020-00352-w.
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.
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.
PaO/FiO 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.
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.
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。实验性治疗策略已针对在ARDS中紊乱的保护系统，如表面活性剂。尽管ARDS中表面活性剂替代疗法（SRT）的结果不一，但关于表面活性剂的给药时机和剂量策略的问题仍未完全得到解答。此外，文献中真正具有临床相关性的ARDS模型很少。我们研究的主要目的是创建一个需要体外膜肺氧合（ECMO）的具有临床相关性、可重复的重症ARDS模型。其次，我们试图将该模型作为一个平台来评估一种包括盐水灌洗和SRT的支气管镜干预措施。
对约克夏猪进行气管切开并插管以进行静脉-静脉ECMO支持，然后通过支气管镜用胃液使其肺损伤。损伤后将动物随机分为两组，在ECMO期间，一组接受支气管镜盐水灌洗联合SRT及肺复张手法（治疗组，n = 5），另一组仅接受肺复张手法（对照组，n = 5）。
对照组和治疗组在误吸损伤后的氧合指数（PaO/FiO）分别为62.6±8 mmHg和60.9±9.6 mmHg（p = 0.95），均满足重症ARDS标准。ECMO逆转了严重低氧血症。在ECMO期间进行盐水灌洗和SRT治疗后，治疗组和对照组的肺生理和血流动力学参数无显著差异。
建立了一个需要ECMO的具有临床相关性的重症ARDS猪模型。与对照组相比，ECMO期间的支气管镜盐水灌洗和SRT未提供显著的生理益处。
