Review: In acutely ill adults, liberal oxygen therapy increases mortality and does not reduce disability compared with conservative oxygen therapy.
Chu DK, Kim LH, Young PJ, 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 Apr 28;391(10131):1693-1705. doi: 10.1016/S0140-6736(18)30479-3. Epub 2018 Apr 26.

BACKGROUND: Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults.

METHODS: In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged =18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697.

FINDINGS: 25 randomised controlled trials enrolled 16?037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO2] across trials, 96% [range 94-99%, IQR 96-98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03-1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01-1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00-1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses.

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

FUNDING: None.

Ratings
Specialty Area Score
Emergency Medicine
Hospital Doctor/Hospitalists
Internal Medicine
Intensivist/Critical Care
Respirology/Pulmonology
Neurology
Cardiology
Comments from MORE raters

Cardiology

The info is important that in acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. The caveat that supplemental oxygen might become unfavorable above an SpO2 range of 94–96% is important as well. That conservative administration of oxygen therapy should be the choice of O2 use is important.

Emergency Medicine

Important addition to the "less is more" approach to medicine. There have been several similar publications in the past few months for acute coronary syndrome. A systematic review is higher-quality evidence than single studies and is now expanded to include sepsis, stroke, and trauma, but probably less newsworthy now than would have been the case last year.

For many providers, the thought of applying oxygen to patients is not considered an action that could affect patients in a negative way. This review should make all providers stop and consider whether their patient truly needs oxygen.

This is an important article because it's highly relevant to EM practice and because the data clearly demonstrate that standard practice (supplementing with a lot of oxygen) is associated with increased mortality.

Hospital Doctor/Hospitalists

As true of any systematic review, this one is not free from bias; however, it is definitely worth reading a publication that reviews the benefits of the judicious use of supplemental oxygen. The RR is very close to 1, with a 95% CI approaching 1 in all groups. Although valid, this makes a weak argument in favor of conservative oxygen therapy for decreasing mortality.

Wow. Very important study that will get a lot of folks talking. In hospital, the viewpoint (that the authors describe) is that oxygen is at worst not helpful, but it is not harmful. It is a common to hear clinicians say, "just leave the oxygen on" for longer because of this. This could be a real practice-changing article. In addition, backing off on using supplemental oxygen would save resources.

Intensivist/Critical Care

I'm unsure if this is newsworthy due to the extreme variations in study parameters (method of estimating actual FiO2, some very narrow differences between FiO2 of two groups) not accounted for. Controlling for severity of illness by ICU v non-ICU seems too broad; sicker patients will have higher FiO2 needs regardless of location.

Very important meta-analysis as previous meta-analyses about hyperoxia in critical care settings focused on subgroups (e.g post-cardiac arrest and post-MI). This meta-analysis examines studies across most critical care patient populations, so the results are very important.

This paper could change my clinical practice and my attitude towards the O2 supplement.

Internal Medicine

The only previous randomized data on this subject that I'm aware of is a trial in emergent COPD patients, which also showed harm.

Very important article with high clinical impact.

Neurology

The reflexive and often unnecessary use of oxygen has long been an irritant to me. It is such an ingrained practice, however, that I fear it will be difficult to eradicate, in spite of a growing body of actual evidence that it can be not merely unhelpful, but frankly harmful.

Respirology/Pulmonology

A large detailed meta-analysis that found increased mortality in acutely ill hospitalized patients treated with a liberal oxygen policy. This study adds credence to the idea that more may not be beneficial. The reasons for this finding cannot be gleaned from this study, and the definition of "liberal" oxygen therapy is vague. Nonetheless, it would seem reasonable to avoid supplemental oxygen in the absence of true hypoxemia. This will certainly require further study to better define when to avoid hyperoxia.

This is a great synthesis of the data suggesting that hyperoxia may be detrimental to patients. Much of these data are emerging, and I think this is an area of critical care with which most clinicians are not familiar. As such, I think most intensivists probably don't know this. Given the quality of the data, I think the results are provocative, but probably not quite robust enough to be practice-changing - not quite yet.

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