Alnababteh Muhtadi, Cui Xizhong, Jeakle Mark, Li Yan, Terry Nancy, Gamble Tom, Sun Junfeng, Kanth Shreya, Eichacker Peter Q, Torabi-Parizi Parizad
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
NIH Library, Office of Research Services, National Institutes of Health, Bethesda, MD, 20892, USA.
Intensive Care Med Exp. 2025 Jul 18;13(1):74. doi: 10.1186/s40635-025-00781-5.
Controlled clinical trials investigating ongoing questions about extracorporeal membrane oxygenation (ECMO) for patients with the acute respiratory distress syndrome (ARDS), including what the optimal mechanical ventilation (MV) tidal volume (TV) strategies are and whether ECMO potentiates injurious host responses, are difficult. We therefore conducted a systematic literature search and review to characterize studies investigating ECMO in adult animal lung injury models and to determine whether they inform these questions.
A systematic literature search with relevant search terms was conducted of four data bases through 2/2/24.
Forty-five studies met inclusion criteria, and most parameters examined were represented similarly in studies with (n = 24) or without (n = 21) severe ARDS PaO/FiOs levels (≤ 100 mmHg or > 100 mmHg). Overall, while only 11 studies were published from 1971 to 2005, 5, 8, and 11 were published in subsequent 5-year periods up to 2020 and then 10 through 2/2/24 (Figure 1). Most studies investigated pig or sheep models (n = 32), but since 2016, six studies employed rat models. Eighteen studies administered lung lavage alone or with another lung injury challenge (17 with PaO/FiOs ≤ 100) and 9 used oleic acid. Although seven studies administered lipopolysaccharide, very different from clinical ARDS only one used a bacterial and none a viral challenge. Thirty-two studies employed V-V ECMO. The most frequent duration of ECMO investigated was 24 h in 16 studies but only 2 studies investigated longer periods (48 and 96 h). Differences in study questions, methodologies and outcome measures precluded formal meta-analysis. However, overall in studies that compared mechanical ventilation alone (MV) to ECMO groups or that compared differing ECMO groups: in 5 studies ECMO supported tidal volume reductions that approached apneic levels in 2; all but 1 of 10 studies indicated that ECMO with or without TV reductions either did not increase or reduced lung injury measures; 2 studies did while 4 did not find that ECMO aggravated molecular or cellular markers of inflammation; and only 2 studies examined host thrombotic responses with ECMO. Fig. 1 Flow diagram for the literature search CONCLUSION: Animal models to date have addressed important questions facing ECMO use for ARDS, but ones more closely simulating ARDS in patients appear warranted.
针对急性呼吸窘迫综合征（ARDS）患者体外膜肺氧合（ECMO）相关问题进行的对照临床试验颇具难度，这些问题包括最佳机械通气（MV）潮气量（TV）策略是什么，以及ECMO是否会增强有害的宿主反应。因此，我们进行了一项系统的文献检索和综述，以描述在成年动物肺损伤模型中研究ECMO的研究，并确定它们是否能解答这些问题。
截至2024年2月2日，使用相关检索词对四个数据库进行了系统的文献检索。
45项研究符合纳入标准，大多数研究中所检查的参数在伴有（n = 24）或不伴有（n = 21）严重ARDS（动脉血氧分压/吸入氧分数值[PaO₂/FiO₂]水平≤100 mmHg或>100 mmHg）的研究中表现相似。总体而言，虽然1971年至2005年仅有11项研究发表，但在随后至2020年的5年期间分别有5项、8项和11项研究发表，然后截至2024年2月2日又有10项研究发表（图1）。大多数研究调查了猪或羊模型（n = 32），但自2016年以来，有6项研究采用了大鼠模型。18项研究单独给予肺灌洗或联合另一种肺损伤刺激（17项研究中PaO₂/FiO₂≤100），9项研究使用油酸。虽然有7项研究给予脂多糖，但与临床ARDS差异很大，只有1项研究使用细菌刺激，没有一项研究使用病毒刺激。32项研究采用静脉-静脉ECMO。所研究的ECMO最常见持续时间为24小时（16项研究），但只有2项研究调查了更长时间（48小时和96小时）。研究问题、方法和结局指标的差异妨碍了正式的荟萃分析。然而，总体而言，在将单纯机械通气（MV）与ECMO组进行比较或比较不同ECMO组的研究中：在5项研究中，ECMO支持潮气量降低，其中2项研究接近窒息水平；10项研究中除1项外，所有研究均表明，无论是否降低潮气量，ECMO要么不会增加，要么会降低肺损伤指标；2项研究显示ECMO会加重炎症的分子或细胞标志物，而4项研究未发现这一点；只有2项研究检查了ECMO的宿主血栓形成反应。图1文献检索流程图结论：迄今为止，动物模型已经解决了ECMO用于ARDS面临的重要问题，但似乎有必要建立更接近模拟患者ARDS的模型。
