Oxygen targets in critically ill patients: from pathophysiology to population enrichment strategies

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.