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N Engl J Med. 2019 Oct 14. doi: 10.1056/NEJMoa1903297. [Epub ahead of print]

Conservative Oxygen Therapy during Mechanical Ventilation in the ICU.

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From the Medical Research Institute of New Zealand (D.M., R. Beasley, R.F., C.M., S.M., P.Y.) and the Intensive Care Unit, Wellington Hospital (P.Y.), Wellington, the Intensive Care Unit, Hawkes Bay Hospital, Hastings (R.F.), and the Department of Critical Care Medicine (C.M.) and the Cardiothoracic and Vascular Intensive Care Unit (S.M.), Auckland City Hospital, Auckland - all in New Zealand; the Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC (R. Bellomo, M.B., V.K., N.L.), the Intensive Care Unit, Austin Hospital, Heidelberg, VIC (R. Bellomo, G.E.), the University of Melbourne (R. Bellomo, M.B., A.D.) and the Intensive Care Unit, Royal Melbourne Hospital (A.D.), Parkville, VIC, the Division of Critical Care and Trauma, George Institute for Global Health, Sydney (S.F.), the Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, St. Leonards, NSW (S.F.), the Intensive Care Unit, Fiona Stanley Hospital, Murdoch, WA (E.L.), the Intensive Care Unit, John Hunter Hospital, New Lambton Heights, NSW (R.P.), and the School of Medicine and Public Health, University of Newcastle, Newcastle, NSW (R.P.) - all in Australia.



Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation).


We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28.


The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of -0.3 days (95% confidence interval [CI], -2.1 to 1.6; P = 0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37).


In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days. (Funded by the New Zealand Health Research Council; ICU-ROX Australian and New Zealand Clinical Trials Registry number, ACTRN12615000957594.).


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