Abstract: We included 10 RCTs (1458 participants), seven of which reported relevant outcomes for this review (1285 participants). All included trials had an overall high risk of bias, whilst two trials had a low risk of bias for all domains except blinding of participants and personnel. Meta-analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding mortality at the time point closest to three months (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.01 to 1.37; I2 = 0%; 4 trials; 1135 participants; very low-certainty evidence). Meta-analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding serious adverse events at the time point closest to three months (estimated highest proportion of specific serious adverse events in each trial RR 1.13, 95% CI 1.04 to 1.23; I2 = 0%; 1234 participants; 6 trials; very low-certainty evidence). These findings should be interpreted with caution given that they are based on very low-certainty evidence. None of the included trials reported any data on quality of life at any time point. Meta-analysis indicated no evidence of a difference between higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation on lung injury at the time point closest to three months (estimated highest reported proportion of lung injury RR 1.03, 95% CI 0.78 to 1.36; I2 = 0%; 1167 participants; 5 trials; very low-certainty evidence). None of the included trials reported any data on acute myocardial infarction or stroke, and only one trial reported data on the effects on sepsis. We are very uncertain about the effects of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU on all-cause mortality, serious adverse events, and lung injuries at the time point closest to three months due to very low-certainty evidence. Our results indicate that oxygen supplementation with higher versus lower fractions or oxygenation targets may increase mortality. None of the trials reported the proportion of participants with one or more serious adverse events according to the ICH-GCP criteria, however we found that the trials reported an increase in the number of serious adverse events with higher fractions or oxygenation targets. The effects on quality of life, acute myocardial infarction, stroke, and sepsis are unknown due to insufficient data.

Plain-language summary: We identified 10 randomized controlled trials (studies where participants are randomly allocated to either an experimental or a control group) involving 1458 participants up to December 2018. Seven of the trials (1285 participants) provided findings on the number of deaths, serious adverse events, and lung injuries in the three months following oxygen therapy in the ICU. Lung injury was measured according to participants developing acute respiratory distress syndrome or pneumonia. Five trials included adults admitted to an ICU caring for patients with a range of serious health conditions and one to a surgical ICU. Two trials involved adults with traumatic brain injury; one trial adults after cardiac arrest and resuscitation; and one trial adults with stroke. All participants in six trials received invasive mechanical ventilation directly through a tube into the main airway. In one trial some of the participants were on mechanical ventilation, whilst others received non-invasive oxygen administration. Three trials involved adults receiving non-invasive oxygen. All trials compared more with less oxygen, however using very different levels of oxygen supplementation. Oxygen therapy was given for timeframes ranging from one hour to the length of hospital admission. We are uncertain about the effects of higher levels of oxygen as our findings are based on very low-certainty evidence. We found no evidence for a beneficial effect of higher compared with lower supplemental oxygen levels for adults admitted to ICU. Higher levels of oxygen may have increased the risk of death (4 trials; 1135 participants) and serious adverse events (6 trials; 1234 participants). There was no evidence of a difference in lung injuries with the use of higher supplemental oxygen compared with lower supplemental oxygen, but the evidence is very uncertain (5 trials; 1167 participants). None of the included trials reported on quality of life at any time point, acute myocardial infarction, and stroke. Only one trial reported on sepsis. The numbers of participants enrolled in the trials were too small to permit a definitive judgement about the review findings. The trials varied in the types of illness of the participants, their associated clinical care, disease severity, the targets for how much oxygen was given, and for how long. Two of the trials had a low risk of bias other than for lack of blinding of participants and personnel. Overall all included trials had a high risk of bias.