REBEL Cast Ep 55 – Hyperoxia in the Critically Ill

Background: Critically ill patients come to the ED all the time and it is almost reflexive to liberally administer oxygen in these acutely ill patients.  Many providers may consider supplemental oxygen a harmless and potentially beneficial therapy in these patients, irrespective of the presence or absence of hypoxemia (i.e. hyperoxia). There have been several trials (Stroke Oxygen Study, Oxygen in AMI, & Oxygen in the ICU) that have shown harm with hyperoxia in the critically ill. This paper is a systematic review and meta-analysis evaluating the evidence base for liberal versus conservative oxygen therapy in this patient population.

REBEL Cast Episode 55 – Hyperoxia in the Critically Ill

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Chu DK et al. Mortality and Morbidity in Acutely Ill Adults Treated with Liberal Versus Conservative Oxygen Therapy (IOTA): A Systematic Review and Meta-Analysis. Lancet 2018. [Epub Ahead of Print]

What They Did: This was a systematic review and meta-analysis of multiple databases  ( Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and WHO International Clinical Trials Registry) of randomized controlled trials comparing liberal vs conservative oxygen therapy in acutely ill adults. Across studies the baseline median Sp02 in the liberal oxygen arm was 96.4% (Range 94.0 – 99.0%)

Outcomes: The main outcomes were mortality, in-hospital, at 30 days, and longest follow up and morbidity, defined as disability at the longest follow-up, risk of hospital acquired pneumonia, any hospital acquired infection, and length of hospital stay

Inclusion: Randomized controlled trials that compared the use of liberal vs conservative oxygen therapy in acutely ill adults (age ≥18 years) and reported an outcome of interest.  Acutely ill was defined as requiring non-elective hospital admission and the potential to be exposed to supplemental oxygen.  Critical illness was defined as an admission to an ICU.

Exclusion: Studies in patients under the age of 18 years or with chronic respiratory diseases, psychiatric diseases, on extracorporeal life support,  treatment with hyperbaric oxygen therapy, or elective surgeries were excluded.  The authors also excluded observational trials and trials in patients who were pregnant.

Results: 25 RCTs enrolling 16,037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, cardiac arrest , and or emergency surgery were included in this evaluation

  • There was no difference in disability, hospital acquired infections, hospital acquired pneumonias, or length of hospital stay


  • This study asks an important clinical question and answers it with a comprehensive and up to date literature search.
  • The broad eligibility criteria and robust methodology increase the generalizability of this study
  • The quality of evidence was evaluated using the grading recommendations assessment, development, and evaluation (GRADE) approach
  • The risk of bias of included studies was analyzed using a Cochrane risk of bias assessment tool. If any one domain was biased, this study was considered to be at high risk of bias
  • This is the first study to systematically review and synthesize randomized control trials evaluating the efficacy and safety of liberal versus conservative oxygen therapyacross a broad range of acute illnesses
  • Heterogeneity between studies was low for all mortality outcomes
  • Evidence quality was high among the majority of the included studies


  • There was a huge variation in study settings and definitions of liberal and conservative oxygen therapy
  • Only a small number of studies reported cause-specific mortality or uniform morbidity outcomes, therefore making it impossible to identify precise mechanisms of harm of hyperoxia
  • Heterogeneity was high for morbidity outcomes


  • This data provides some evidence that setting threshold spans of SpO2 should range from 94 – 96%. This range was derived from the lower 95% CI limit and the median baseline SpO2 in the liberal oxygen group. The 2015 Thoracic Society of Australia and New Zealand recommend oxygen titration to a maximum SpO2 of 96%.
  • This trial challenges the preconceived benefits of hyperoxia in stroke improves disability outcomes. The prior theory was that hyperoxia helps salvage the penumbra area of stroke
  • Interestingly, on the back of low quality evidence there was a reduction in the risk of surgical site infections in patients undergoing emergency surgery with liberal oxygen use. This should be balanced with the high quality of evidence showing an increase in mortality in patients undergoing liberal oxygen therapy compared to conservative oxygen therapy.

Author Conclusion: “In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes.  Supplemental oxygen might become unfavorable above and SpO2 range of 94 – 96%.  These results support the conservative administration of oxygen therapy.”

Clinical Take Home Point: In critically ill adults we should avoid hyperoxia as this increases mortality.  Instead we should aim for a target SpO2 of 94 – 96% in these patients.


  1. Chu DK et al. Mortality and Morbidity in Acutely Ill Adults Treated with Liberal Versus Conservative Oxygen Therapy (IOTA): A Systematic Review and Meta-Analysis. Lancet 2018. [Epub Ahead of Print]

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

Cite this article as: Salim Rezaie, "REBEL Cast Ep 55 – Hyperoxia in the Critically Ill", REBEL EM blog, July 9, 2018. Available at:

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