Oxygen targets in critically ill patients: from pathophysiology to population enrichment strategiesRipa, Claudio1;Munshi, Laveena2,3,4;Kuebler, Wolfgang M.5,6,7,8,9;Magliocca, Aurora10;Taccone, Fabio S.11;Ware, Lorraine B.12,13;Citerio, Giuseppe1,14;Laffey, John G.15,16;Rezoagli, Emanuele 1School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy 2Interdepartmental Division of Critical Care Medicine, Sinai Health System/University Health Network, University of Toronto, Toronto, Canada 3Department of Medicine, Sinai Health System and University Health Network, Toronto, Canada 4Mount Sinai Hospital, Toronto, Canada 5Institute of Physiology, Charité-Universitätsmedizin, Berlin, Germany 6German Center for Cardiovascular Research, Berlin, Germany 7Department of Surgery, University of Toronto, Toronto, Canada 8Department of Physiology, University of Toronto, Toronto, Canada 9Keenan Research Center, St Michael’s Hospital, Toronto, Canada 10Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy 11Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium 12Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA 13Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA 14Department of Neuroscience, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy 15Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway, Ireland 16Anaesthesia, School of Medicine, College of Medicine, Nursing and Health Sciences, and CÚRAM Center for Research in Medical Devices, University of Galway, Galway, Ireland 17Department of Emergency and Intensive Care, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, Monza, Italy Abstract Oxygen supplementation is widely used to enhance oxygen delivery and to treat or prevent hypoxia; however, it requires careful management to avoid the harmful effects of excessive oxygen exposure. Both hyperoxia (inspiratory oxygen fraction exceeding 0.21) and hyperoxemia (arterial oxygen tension oxygen partial pressure [PaO2] > 100 mmHg) can contribute to lung injury, promote systemic vasoconstriction, and increase the production of reactive oxygen species, which can impair macromolecular and cellular functions. Conversely, in certain situations, hyperoxemia may provide benefits, such as hemodynamic stabilization in hyperdynamic shock, immunomodulation, and bactericidal effects. The literature presents conflicting evidence regarding the impact of different oxygen targets (i.e., PaO2 and/or peripheral saturation of oxygen [SpO2]) on both short- and long-term outcomes in patients with acute critical conditions, such as acute respiratory distress syndrome, sepsis, cardiac arrest, and acute central nervous system injuries. These discrepancies may stem from the small differences between the oxygenation targets used in randomized trials, the physiological limitations of PaO2 and SpO2 targets, which reflect blood oxygen content rather than oxygen delivery, the lack of measurements of microvascular function or oxygen delivery, and the heterogeneity in treatment response. Furthermore, advanced analytical methods (e.g., machine learning) are emerging as promising tools to implement population enrichment strategies. By refining patient sub-group identification, these approaches can significantly optimize precision medicine, enabling more personalized oxygen therapy tailored to individual patient characteristics. 氧疗被广泛用于改善氧供及治疗或预防低氧血症，但需谨慎管理以避免高氧暴露的危害。无论是高氧吸入（吸入氧分数>0.21）还是高氧血症（动脉血氧分压[PaO₂]>100 mmHg），均可能引发肺损伤、促进全身血管收缩、增加活性氧生成，进而损害大分子及细胞功能。然而在某些情况下，高氧血症可能具有获益效应，包括：稳定超动力型休克患者的血流动力学、发挥免疫调节及杀菌作用。 关于不同氧疗目标值（PaO₂和/或外周血氧饱和度[SpO₂]）对急性呼吸窘迫综合征、脓毒症、心脏骤停及急性中枢神经系统损伤等急危重症患者短期与长期预后的影响，现有文献证据存在矛盾。这些矛盾可能源于： 值得注意的是，机器学习等先进分析方法正成为实施人群富集策略的有力工具。通过优化患者亚组识别，这些方法可显著提升精准医疗水平，为基于个体特征的个性化氧疗提供新范式。 |