Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.
Supplemental oxygen is one of the functions provided by modern mechanical ventilation and can be adjusted according to the patient’s needs. While clinicians have historically prioritized avoiding hypoxemia, a growing body of evidence indicates that excessive oxygen exposure carries its own risks and that the fraction of inspired oxygen (FiO2) deserves the same disciplined titration during mechanical ventilation that is afforded to tidal volume and positive end-expiratory pressure (PEEP).
The physiological rationale for caution is well established. High FiO2 can cause reabsorption atelectasis in lung units with low ventilation-perfusion ratios, an effect that can be mitigated with adequate PEEP (Pham et al., 2017). Beyond the lungs, hyperoxia reduces parasympathetic tone and cardiac output, increases vascular resistance, and produces vasoconstrictive effects on cerebral and coronary perfusion (Pham et al., 2017). Reactive oxygen species generation and oxidative stress are additional mechanisms by which sustained hyperoxemia may cause harm (Suzuki et al., 2018). Several observational studies have linked hyperoxemia to increased mortality in specific populations, including patients resuscitated from cardiac arrest or stroke, even as clinicians remain more attuned to hypoxemia than to its opposite (Pham et al., 2017).
Despite this rationale, liberal oxygen administration remains standard practice in many settings, with the consequences of hypoxemia being much clearer. A multicenter cross-sectional study of over 1,400 patients undergoing general anesthesia in Japan found that potentially preventable hyperoxemia occurred in 83% of cases, and nearly a third of patients met criteria for substantial oxygen exposure (Suzuki et al., 2018). One-lung ventilation was the strongest independent predictor of excessive exposure, with an adjusted odds ratio exceeding 13, while volume-controlled ventilation and higher PEEP were associated with reduced exposure (Suzuki et al., 2018). Notably, oxygen settings were rarely adjusted once established in these cases, suggesting that hyperoxemia may reflect inattention rather than deliberate clinical judgment.
Clinical trial evidence on conservative oxygen strategies, however, has been mixed. The ICU-ROX trial randomized 1,000 critically ill adults expected to require mechanical ventilation to conservative versus usual oxygen therapy, targeting an SpO2 ceiling of 97% in the conservative arm. Although a clear separation in oxygen exposure was achieved between groups, there was no significant difference in ventilator-free days or 90- and 180-day mortality (ICU-ROX Investigators, 2020). A prespecified subgroup of patients with suspected hypoxic-ischemic encephalopathy showed a signal toward benefit with conservative therapy, though this finding was considered hypothesis-generating rather than definitive (ICU-ROX Investigators, 2020). These results tempered enthusiasm generated by an earlier single-center trial and underscored that the optimal oxygen target, and the population most likely to benefit from restriction, remain unresolved (ICU-ROX Investigators, 2020).
Current consensus favors a moderate approach: targeting an SpO2 of roughly 92% to 96% during invasive ventilation, using the lowest FiO2 necessary to meet that goal, and recognizing that in patients with substantial shunt, further increases in FiO2 yield diminishing returns on arterial oxygenation (Pham et al., 2017; Goligher et al., 2016). Emerging tools, including electrical impedance tomography, esophageal manometry, and artificial intelligence–assisted monitoring, may eventually allow oxygenation to be more easily individualized alongside other ventilator settings as part of a broader personalized ventilation strategy (Rubulotta et al., 2024).
Inspired oxygen concentration during mechanical ventilation is an important therapeutic variable with a risk-benefit profile that warrants consideration. While randomized data have not yet demonstrated a definitive mortality benefit from conservative oxygen strategies across populations, the physiological rationale, observational associations, and demonstrated prevalence of unrecognized hyperoxemia together support routine, deliberate titration of FiO2 rather than passive, fixed administration.
References
- Goligher, E. C., Ferguson, N. D., & Brochard, L. J. (2016). Clinical challenges in mechanical ventilation. The Lancet, 387(10030), 1856–1866. https://doi.org/10.1016/S0140-6736(16)30176-3
- ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. (2020). Conservative oxygen therapy during mechanical ventilation in the ICU. New England Journal of Medicine, 382(11), 989–998. https://doi.org/10.1056/NEJMoa1903297
- Pham, T., Brochard, L. J., & Slutsky, A. S. (2017). Mechanical ventilation: State of the art. Mayo Clinic Proceedings, 92(9), 1382–1400. https://doi.org/10.1016/j.mayocp.2017.05.004
- Rubulotta, F., Blanch Torra, L., Naidoo, K. D., Soliman Aboumarie, H., Mathivha, L. R., Asiri, A. Y., Sarlabous Uranga, L., & Soussi, S. (2024). Mechanical ventilation, past, present, and future. Anesthesia & Analgesia, 138(2), 308–325. https://doi.org/10.1213/ANE.0000000000006701
- Suzuki, S., Mihara, Y., Hikasa, Y., Okahara, S., Ishihara, T., Shintani, A., & Morimatsu, H. (2018). Current ventilator and oxygen management during general anesthesia: A multicenter, cross-sectional observational study. Anesthesiology, 129(5), 909–919. https://doi.org/10.1097/ALN.0000000000002181