A systematic review of adult animal models investigating ECMO use for ARDS: where to from here

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 PaO₂/FiO₂s 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 PaO₂/FiO₂s ≤ 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.