Optimal oxygenation in the intensive care unit: what recent trials do-and do not-tell us

Oxygen therapy is one of the most widely used interventions in critical care. Numerous observational studies and randomized controlled trials (RCTs) have evaluated conservative versus liberal oxygenation strategies, yet their results remain inconsistent, a pattern commonly observed in large clinical trials across multiple fields. Recent advances in intensive care unit practices further complicate the interpretation of prior findings, highlighting the need for a clearer framework to interpret oxygenation targets. This narrative review summarizes major observational studies, RCTs, and meta-analyses evaluating oxygenation strategies in critically ill patients. We examine variation in study designs, target and achieved oxygenation levels, and evolving critical care practices. Physiological principles, including oxygen delivery, oxygen utilization, and the oxyhemoglobin dissociation curve, are applied to interpret current evidence and define clinically meaningful safety margins, while acknowledging the limitations of interpreting heterogeneous trial and meta-analytic results. Recent RCTs have found relatively small differences in oxygenation between study groups; both conservative and liberal oxygenation targets are generally within a safe physiological range. However, evidence from the LOCO2 trial indicates excessively low targets may be harmful, suggesting a safer lower limit of approximately peripheral oxygen saturation (SpO2) 92%-93%. Retrospective studies indicate acceptable outcomes with arterial oxygen partial pressure (PaO2) values up to approximately 120 mm Hg. Because the upper portion of the oxyhemoglobin dissociation curve is flat, SpO2 cannot reliably detect hyperoxemia. Rather than determining the superiority of conservative or liberal oxygenation strategies, current evidence supports defining a practical therapeutic window. For most critically ill patients, an SpO2 range of 92-97% likely represents a safe and clinically meaningful target.