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Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis

Derek K Chu, Lisa H-Y Kim, Paul J Young, Nima Zamiri, Saleh A Almenawer, Roman Jaeschke, Wojciech Szczeklik, Holger J Schünemann, John D Neary, Waleed Alhazzani
Lancet 2018 April 28, 391 (10131): 1693-1705
29726345

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.

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William Hewgley

16,037 pt from 25 trials. Variable pathologies admitted to ICU. 2 trials dominated in numbers, MI and stroke. Performed subgroup analysis including emerg surgery. Elective surgery excluded. Excluded baseline hypoxemic pt.

Considerable variability between definitions of liberal vs conservative. Generally NC or FM vs room air. Some fixed dose and some O2 target.

Liberal O2 therapy increases mortality at all time points (HR 1.1 NNTH 71).

Liberal O2 therapy also increases mortality in EGS subgroup.

Liberal O2 therapy may decrease HAI in EGS pt but not medical pt. (RR 0.5) bias? Imprecision?

Increasing Sp02 modestly increases Pa 02 dramatically -> ROS. Liberal therapy may decrease vigilance.

Threshold for harm unclear but probably between 94-96 on O2.

Low quality evidence for decreased risk of infection. Increased ROS -> better neutrophil activity?

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