Guiding Treatment Decisions in Pediatric ECMO: The Role of Lung Biopsy in Unclear Respiratory Failure

Introduction: Extracorporeal membrane oxygenation (ECMO) represents an established rescue therapy for children with severe, refractory respiratory failure. However, in some cases the underlying pulmonary pathology remains unclear with no clinical improvement despite maximal supportive therapy. In this situation, lung biopsy may provide decisive diagnostic information to distinguish irreversible developmental lung disorders from potentially treatable lung diseases. Although experience with lung biopsy during pediatric ECMO is limited, published case series suggest a high diagnostic relevance and pivotal impact on clinical decision-making. Case Presentation: Here, we report three pediatric patients with severe respiratory failure requiring ECMO support in whom lung biopsy was performed due to unclear etiology and lack of clinical improvement. In two cases, histopathological examination revealed alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). Given the poor prognosis and lack of curative treatment available, the biopsy findings led to a multidisciplinary decision to withdraw life-sustaining therapy in both cases. In the third child, lung biopsy demonstrated pulmonary interstitial glycogenosis, a rare but potentially treatable interstitial lung disease of infancy. Based on this diagnosis, ECMO support was continued, resulting in a favorable clinical outcome. Discussion: In all three patients, lung biopsy during ongoing ECMO proved to be essential for further management. The identification of ACD/MPV enabled an informed and ethically sound decision to limit therapy, avoiding prolonged non-beneficial treatment. Conversely, the diagnosis of pulmonary interstitial glycogenosis justified continuation of aggressive supportive care and was associated with good outcome in this case. While the procedure carries inherent risks, particularly bleeding, our experience supports its use in carefully selected patients. When performed in specialized centers, lung biopsy during pediatric ECMO may represent a key diagnostic tool guiding patient-centered and prognostically appropriate care. However, current evidence is limited to few case series and single-center experiences. In our opinion further systematic study and international data acquisition in this field is required for evaluation of complications and therapeutic consequences to improve evidence-based decision-making in this highly vulnerable patient population. Publication History Article published online: 26 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany