Pulmonary endarterectomy (PEA) remains the curative surgical option for chronic thromboembolic pulmonary hypertension (CTEPH), a condition requiring precise cardiopulmonary bypass (CPB) management to balance cerebral protection, myocardial preservation, and right-ventricular recovery. Historically based on deep hypothermic circulatory arrest (DHCA), PEA perfusion strategies have evolved toward moderate hypothermia, intermittent reperfusion, and goal-directed perfusion (GDP) guided by oxygen delivery (DO₂i) and metabolic indices. The advent of continuous perfusion monitoring, automated temperature regulation, and algorithm-driven management heralds a new era of precision perfusion in PEA. This narrative review and perspective integrates evidence from 24 peer-reviewed publications (2006-2025), including randomized controlled trials, multicenter observational studies, and technical reports. A systematic literature search was conducted in PubMed, Scopus, and Google Scholar using combinations of the keywords: pulmonary endarterectomy, cardiopulmonary bypass, goal-directed perfusion, oxygen delivery, hypothermia, and ECMO. Reference lists of eligible articles were cross-checked for additional sources. Inclusion criteria were: studies addressing CPB techniques or monitoring during PEA; data on temperature strategy, perfusion parameters, or metabolic guidance; and English-language full-text publications. Data were extracted and narratively synthesized to identify recurring patterns, innovations, and unmet needs in perfusion management. Findings confirmed the clinical equivalence between DHCA and antegrade cerebral perfusion in neurological outcomes and supported the safety of moderate hypothermia (20-24 °C) with intermittent reperfusion. Contemporary protocols adopt DO₂i targets ≥ 280-330 mL/min/m², integrating temperature-adjusted algorithms for individualized perfusion. Albumin-based prime and osmotic agents improve hemodynamic and cerebral stability, while Custodiol/HTK ensures sustained myocardial protection. ECMO is required in 7-10% of cases, predominantly for refractory right-ventricular dysfunction or reperfusion edema, with early initiation improving survival. The evolution of perfusion in PEA reflects a paradigm shift from empiric hypothermic models to dynamic, goal-directed, and technology-assisted perfusion. Real-time DO₂i monitoring, temperature-adjusted control, and algorithm-driven decision support are redefining intraoperative management. The next challenge lies in standardizing perfusion protocols and integrating automated systems capable of maintaining metabolic homeostasis throughout CPB. Collaborative multicenter studies and registries are warranted to validate these approaches and establish evidence-based guidelines for contemporary PEA perfusion.
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