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This review describes the intricate physiological interactions involved in the application of extracorporeal therapy, with specific focus on cardiopulmonary relationships. Extracorporeal therapy significantly influences cardiovascular and pulmonary physiology, highlighting the necessity for clinicians to understand these interactions for improved patient care. Veno-arterial extracorporeal membrane oxygenation (veno-arterial ECMO) unloads the right ventricle and increases left ventricular (LV) afterload, potentially exacerbating LV failure and pulmonary edema. Veno-venous (VV) ECMO presents different challenges, where optimal device and ventilator settings remain unknown. Influences on right heart function and native gas exchange as well as end-expiratory lung volumes are important concepts that should be incorporated into daily practice. Future studies should not be limited to large clinical trials focused on mortality but rather address physiological questions to advance the understanding of extracorporeal therapies. This includes exploring optimal device and ventilator settings in VV ECMO, standardizing cardiopulmonary function monitoring strategies, and developing better strategies for device management throughout their use. In this regard, small human or animal studies and computational physiological modeling may contribute valuable insights into optimizing the management of extracorporeal therapies.

Heart-lung interactions occur due to the mechanical influence of intrathoracic pressure and lung volume changes on cardiac and circulatory function. These interactions manifest as respiratory fluctuations in venous, pulmonary, and arterial pressures, potentially affecting stroke volume. In the context of functional hemodynamic monitoring, pulse or stroke volume variation (pulse pressure variation or stroke volume variability) are commonly employed to assess volume or preload responsiveness. However, correct interpretation of these parameters requires a comprehensive understanding of the physiological factors that determine pulse pressure and stroke volume. These factors include pleural pressure, venous return, pulmonary vessel function, lung mechanics, gas exchange, and specific cardiac factors. A comprehensive knowledge of heart-lung physiology is vital to avoid clinical misjudgments, particularly in cases of right ventricular (RV) failure or diastolic dysfunction. Therefore, when selecting monitoring devices or technologies, these factors must be considered. Invasive arterial pressure measurements of variations in breath-to-breath pressure swings are commonly used to monitor heart-lung interactions. Echocardiography or pulmonary artery catheters are valuable tools for differentiating preload responsiveness from right ventricular failure, while changes in diastolic function should be assessed alongside alterations in airway or pleural pressure, which can be approximated by esophageal pressure. In complex clinical scenarios like ARDS, combined forms of shock or right heart failure, additional information on gas exchange and pulmonary mechanics aids in the interpretation of heart-lung interactions. This review aims to describe monitoring techniques that provide clinicians with an integrative understanding of a patient’s condition, enabling accurate assessment and patient care.