Raffaele Merola, Denise Battaglini, Sung-Min Cho
Despite decades of clinical experience, the physiological rationale for extracorporeal life support (ECLS) in acute respiratory distress syndrome (ARDS) remains incompletely defined. Existing trials have primarily evaluated ECLS as a rescue intervention, with limited attention to the physiological adaptations required to sustain extracorporeal gas exchange. We propose that the maternal-fetal circulation, the only naturally occurring example of prolonged extracorporeal gas exchange, provides a hypothesis-generating physiological analogy. In this paradigm, gas exchange is externalized through a low-resistance, high-flow circuit while systemic physiology reorganizes to unload the native lung. Translating this concept to severe ARDS suggests that ECLS should be viewed not simply as an adjunct to conventional support, but as a transition to an alternative physiological state centered on extracorporeal gas exchange. This perspective may inform physiology-based patient selection, management strategies, and the design of future clinical trials.