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Meta-Analysis
. 2023 Sep 13;9(9):CD012631.
doi: 10.1002/14651858.CD012631.pub3.

Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit

Thomas L Klitgaard  1   2   3 , Olav L Schjørring  1   2   3 , Frederik M Nielsen  1   2   3 , Christian S Meyhoff  4 , Anders Perner  3   5 , Jørn Wetterslev  3   6 , Bodil S Rasmussen  1   2   3 , Marija Barbateskovic  7
Affiliations
Meta-Analysis

Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit

Thomas L Klitgaard et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated review concerning 'Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit'. Supplementary oxygen is provided to most patients in intensive care units (ICUs) to prevent global and organ hypoxia (inadequate oxygen levels). Oxygen has been administered liberally, resulting in high proportions of patients with hyperoxemia (exposure of tissues to abnormally high concentrations of oxygen). This has been associated with increased mortality and morbidity in some settings, but not in others. Thus far, only limited data have been available to inform clinical practice guidelines, and the optimum oxygenation target for ICU patients is uncertain. Because of the publication of new trial evidence, we have updated this review.

Objectives: To update the assessment of benefits and harms of higher versus lower fractions of inspired oxygen (FiO2) or targets of arterial oxygenation for adults admitted to the ICU.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, BIOSIS Previews, and LILACS. We searched for ongoing or unpublished trials in clinical trial registers and scanned the reference lists and citations of included trials. Literature searches for this updated review were conducted in November 2022.

Selection criteria: We included randomised controlled trials (RCTs) that compared higher versus lower FiO2 or targets of arterial oxygenation (partial pressure of oxygen (PaO2), peripheral or arterial oxygen saturation (SpO2 or SaO2)) for adults admitted to the ICU. We included trials irrespective of publication type, publication status, and language. We excluded trials randomising participants to hypoxaemia (FiO2 below 0.21, SaO2/SpO2 below 80%, or PaO2 below 6 kPa) or to hyperbaric oxygen, and cross-over trials and quasi-randomised trials.

Data collection and analysis: Four review authors independently, and in pairs, screened the references identified in the literature searches and extracted the data. Our primary outcomes were all-cause mortality, the proportion of participants with one or more serious adverse events (SAEs), and quality of life. We analysed all outcomes at maximum follow-up. Only three trials reported the proportion of participants with one or more SAEs as a composite outcome. However, most trials reported on events categorised as SAEs according to the International Conference on Harmonisation Good Clinical Practice (ICH-GCP) criteria. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single SAE with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with an SAE in each trial. Two trials reported on quality of life. Secondary outcomes were lung injury, myocardial infarction, stroke, and sepsis. No trial reported on lung injury as a composite outcome, but four trials reported on the occurrence of acute respiratory distress syndrome (ARDS) and five on pneumonia. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single lung injury event with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with ARDS or pneumonia in each trial. We assessed the risk of systematic errors by evaluating the risk of bias in the included trials using the Risk of Bias 2 tool. We used the GRADEpro tool to assess the overall certainty of the evidence. We also evaluated the risk of publication bias for outcomes reported by 10b or more trials.

Main results: We included 19 RCTs (10,385 participants), of which 17 reported relevant outcomes for this review (10,248 participants). For all-cause mortality, 10 trials were judged to be at overall low risk of bias, and six at overall high risk of bias. For the reported SAEs, 10 trials were judged to be at overall low risk of bias, and seven at overall high risk of bias. Two trials reported on quality of life, of which one was judged to be at overall low risk of bias and one at high risk of bias for this outcome. Meta-analysis of all trials, regardless of risk of bias, indicated no significant difference from higher or lower oxygenation strategies at maximum follow-up with regard to mortality (risk ratio (RR) 1.01, 95% confidence interval (C)I 0.96 to 1.06; I2 = 14%; 16 trials; 9408 participants; very low-certainty evidence); occurrence of SAEs: the highest proportion of any specific SAE in each trial RR 1.01 (95% CI 0.96 to 1.06; I2 = 36%; 9466 participants; 17 trials; very low-certainty evidence), or quality of life (mean difference (MD) 0.5 points in participants assigned to higher oxygenation strategies (95% CI -2.75 to 1.75; I2 = 34%, 1649 participants; 2 trials; very low-certainty evidence)). Meta-analysis of the cumulated number of SAEs suggested benefit of a lower oxygenation strategy (RR 1.04 (95% CI 1.02 to 1.07; I2 = 74%; 9489 participants; 17 trials; very low certainty evidence)). However, trial sequential analyses, with correction for sparse data and repetitive testing, could reject a relative risk increase or reduction of 10% for mortality and the highest proportion of SAEs, and 20% for both the cumulated number of SAEs and quality of life. Given the very low-certainty of evidence, it is necessary to interpret these findings with caution. Meta-analysis of all trials indicated no statistically significant evidence of a difference between higher or lower oxygenation strategies on the occurrence of lung injuries at maximum follow-up (the highest reported proportion of lung injury RR 1.08, 95% CI 0.85 to 1.38; I2 = 0%; 2048 participants; 8 trials; very low-certainty evidence). Meta-analysis of all trials indicated harm from higher oxygenation strategies as compared with lower on the occurrence of sepsis at maximum follow-up (RR 1.85, 95% CI 1.17 to 2.93; I2 = 0%; 752 participants; 3 trials; very low-certainty evidence). Meta-analysis indicated no differences regarding the occurrences of myocardial infarction or stroke.

Authors' conclusions: In adult ICU patients, it is still not possible to draw clear conclusions about the effects of higher versus lower oxygenation strategies on all-cause mortality, SAEs, quality of life, lung injuries, myocardial infarction, stroke, and sepsis at maximum follow-up. This is due to low or very low-certainty evidence.

Trial registration: ClinicalTrials.gov NCT02321072.

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Conflict of interest statement

Thomas Lass Klitgaard: Co‐ordinating investigator of the Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU) trial, a randomised clinical trial comparing a higher versus lower oxygenation target in adult patients with hypoxaemic respiratory failure acutely admitted to the intensive care unit. Also, co‐ordinating investigator of the Handling Oxygenation Targets in COVID‐19 (HOT‐COVID) trial, a randomised clinical trial comparing a higher versus lower oxygenation target in adult patients with COVID‐19 and hypoxaemic respiratory failure acutely admitted to the intensive care unit.

Olav Lilleholt Schjørring: Olav's Ph.D. study was funded through a grant from the Innovation Fund Denmark. Furthermore, he was the co‐ordinating investigator of the Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU) trial, a randomised clinical trial comparing a higher versus lower oxygenation target in adult patients with hypoxaemic respiratory failure acutely admitted to the intensive care unit.

Frederik Mølgaard Nielsen: Co‐ordinating investigator of the Handling Oxygenation Targets in COVID‐19 (HOT‐COVID) trial, a randomised clinical trial comparing a higher versus lower oxygenation target in adult patients with COVID‐19 and hypoxaemic respiratory failure acutely admitted to the intensive care unit.

Christian Sylvest Meyhoff: Chief investigator for the VitamIn and oXygen Interventions and Cardiovascular Events (VIXIE) trial (a randomised controlled trial comparing perioperative oxygen fractions); site investigator in the HOT‐ICU trial (a randomised controlled trial investigating oxygenation targets in the intensive care unit); co‐author of several Cochrane Reviews about oxygen therapy; and was the primary investigator of the PROXI trial (a randomised controlled trial comparing perioperative oxygen fractions).

Anders Perner: Anders's institution receives money for research from Ferring Pharmaceuticals and the Novo Nordisk Foundation

Jørn Wetterslev: Jørn is a member of the task force on Trial Sequential Analysis (TSA) at the Copenhagen Trial Unit, developing and programming TSA (see www.ctu.dk/tsa). Jørn was a supervisor for PhD Marija Barbateskovic, and the work concerning the previous version of this review was paid for in part by a grant from Innovation Fund Denmark.

Bodil Steen Rasmussen: Bodil is the sponsor and primary investigator of a randomised clinical trial comparing a higher versus lower oxygenation target in adult patients with hypoxaemic respiratory failure acutely admitted to the intensive care unit (the Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU) trial (NCT03174002)). Bodil is also sponsor and primary investigator of a randomised clinical trial comparing a higher versus lower oxygenation target in adult patients with hypoxaemic respiratory failure acutely admitted to the intensive care unit (the Handling Oxygenation Targets in COVID‐19 (HOT‐COVID) trial (NCT04425031)).

Marija Barbateskovic: Innovation Fund Denmark provided a grant to Centre for Research in Intensive Care (CRIC), which made it possible for Copenhagen Trial Unit as a partner of CRIC to write the primary review during Marija Barbateskovic’s PhD study.

Figures

1
1
2
2
Funnel plot of the risk of mortality at maximum follow‐up. A relative risk (RR) < 1 indicates benefit of higher oxygenation strategies, whilst an RR > 1 indicate benefit of lower. Each circle represents the point estimate of the trials. The black dashed line represent the point estimate for the RR of all‐cause mortality at maximum follow‐up (1.01). Abbreviations: log: natural logarithm; SE: standard error; RR: relative risk.
3
3
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the risk of mortality in trials judged to be at overall low risk of bias. The analysis was based on a mortality in the control group (control event proportion = CEP) of 41.9%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 27.9%. The cumulative Z‐curve crossed the trial sequential monitoring boundaries for futility, and the required information size (RIS) was exceeded.
4
4
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the risk of mortality. The analysis was based on a mortality in the control group (control event proportion = CEP) 38.7%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 41.1%. The cumulative Z‐curve crossed the trial sequential monitoring boundaries for futility, and the required information size (RIS) was exceeded.
5
5
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the risk of mortality. The analysis was based on a mortality in the control group (control event proportion = CEP) of 38.7%, a relative risk increase (RRI) of 10%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 41.1%. Required information size = RIS. The cumulative Z‐curve crossed the trial sequential monitoring boundaries for futility.
6
6
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the risk of mortality. The analysis was based on a mortality in the control group (control event proportion = CEP) of 38.7%, a relative risk reduction (RRR) of 4%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 41.1%. Required information size = RIS. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
7
7
Funnel plot of the highest reported proportion of serious adverse events at maximum follow‐up. A relative risk (RR) < 1 indicates benefit of higher oxygenation strategies, whilst an RR > 1 indicate benefit of lower. Each circle represents the point estimate of the trials. The black dashed line represent the point estimate for the RR of the highest reported proportion of serious adverse events at maximum follow‐up (1.01). Abbreviations: log: natural logarithm; SE: standard error; RR: relative risk.
8
8
Funnel plot of the cumulated number of serious adverse events at maximum follow‐up. A relative risk (RR) < 1 indicates benefit of higher oxygenation strategies, whilst an RR > 1 indicate benefit of lower. Each circle represents the point estimate of the trials. The black dashed line represent the point estimate for the RR of the cumulated number of serious adverse events at maximum follow‐up (1.04). Abbreviations: log: natural logarithm; SE: standard error; RR: relative risk.
9
9
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the highest reported proportion of specific serious adverse events. The analysis was based on a proportion of participants with one or more serious adverse events in the control group (control event proportion = CEP) of 41.1%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 64.0%. The cumulative Z‐curve crossed the boundaries for trial sequential monitoring boundaries for futility, and the required information size (RIS) was exceeded.
10
10
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the highest reported proportion of specific serious adverse events. The analysis was based on a proportion of participants with one or more serious adverse events in the control group (control event proportion = CEP) of 41.1%, a relative risk increase (RRI) of 10%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 64.0%. RIS = required information size. The cumulative Z‐curve crossed the boundaries for trial sequential monitoring boundaries for futility.
11
11
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the cumulated number of serious adverse events. The analysis was based on a proportion of participants with one or more serious adverse events in the control group (control event proportion = CEP) of 71.4%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 87.4%. The cumulative Z‐curve crossed the boundaries for trial sequential monitoring boundaries for futility, and the required information size (RIS) was exceeded.
12
12
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the cumulated number of serious adverse events. The analysis was based on a proportion of participants with one or more serious adverse events in the control group (control event proportion = CEP) of 71.4%, a relative risk increase (RRI) of 10%, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 87.4%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
13
13
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on quality of life. The analysis was based on an observed mean difference of ‐0.5 points, a minimal clinical relevance of ‐7 points, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve crossed the trial sequential monitoring boundaries for futility and the required information size was exceeded.
14
14
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on quality of life. The analysis was based on an observed mean difference of ‐0.5 points, a minimal clinical relevance of ‐7 points, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 20%. RIS = required information size. The cumulated Z‐curve crossed the trial sequential monitoring boundaries for futility.
15
15
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on quality of life. The analysis was based on an observed mean difference of ‐0.5 points, a difference of 1.6 points, a type 1 error level (alpha) of 2.5%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
16
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Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the highest reported proportion of lung injuries. The analysis was based on the highest reported proportion of lung injuries in the control group (control event proportion = CEP) of 10.4%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
17
17
Trial Sequential Analysis of the effects of higher versus oxygenation strategies on the highest reported proportion of lung injuries. The analysis was based on the highest reported proportion of lung injuries in the control group (control event proportion = CEP) of 10.4%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 20%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
18
18
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the highest reported proportion of lung injuries. The analysis was based on the highest reported proportion of lung injuries in the control group (control event proportion = CEP) of 10.4%, a relative risk reduction (RRR) of 15%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
19
19
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the cumulated number of lung injuries. The analysis was based on a cumulated number (control event proportion = CEP) of 10.7%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
20
20
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the cumulated number of lung injuries. The analysis was based on a cumulated number of lung injuries in the control group (control event proportion = CEP) of 10.7%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 20%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
21
21
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the cumulated number of lung injuries. The analysis was based on a cumulated number of lung injuries in the control group (control event proportion = CEP) of 10.7%, a relative risk reduction (RRR) of 20%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
22
22
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the occurrence of stroke. The analysis was based on stroke in the control group (control event proportion = CEP) of 1.7%, a relative risk increase (RRI) of 20%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
23
23
Trial Sequential Analysis of the effects of higher versus lower oxygenation strategies on the occurrence of stroke. The analysis was based on stroke in the control group (control event proportion = CEP) of 1.3%, a relative risk reduction (RRR) of 28%, a type 1 error level (alpha) of 2.0%, a type 2 error level (beta) of 10%, and a diversity of 0%. RIS = required information size. The cumulative Z‐curve did not cross any boundaries for benefit and harm, nor trial sequential monitoring boundaries for futility.
1.1
1.1. Analysis
Comparison 1: Trials at overall low risk of bias, Outcome 1: All‐cause mortality ‐ trials at overall low risk of bias
1.2
1.2. Analysis
Comparison 1: Trials at overall low risk of bias, Outcome 2: Highest proportion of specific serious adverse events ‐ trials at overall low risk of bias
1.3
1.3. Analysis
Comparison 1: Trials at overall low risk of bias, Outcome 3: Cumulated number of serious adverse events ‐ trials at overall low risk of bias
1.4
1.4. Analysis
Comparison 1: Trials at overall low risk of bias, Outcome 4: Highest reported proportion of lung injury ‐ trials at overall low risk of bias
1.5
1.5. Analysis
Comparison 1: Trials at overall low risk of bias, Outcome 5: Cumulated number of lung injury ‐ trials at overall low risk of bias
1.6
1.6. Analysis
Comparison 1: Trials at overall low risk of bias, Outcome 6: Stroke ‐ trials at overall low risk of bias
2.1
2.1. Analysis
Comparison 2: All‐cause mortality, Outcome 1: All‐cause mortality
2.2
2.2. Analysis
Comparison 2: All‐cause mortality, Outcome 2: Subgroup analysis: all‐cause mortality ‐ overall risk of bias
2.3
2.3. Analysis
Comparison 2: All‐cause mortality, Outcome 3: Subgroup analysis: all‐cause mortality ‐ types of oxygen interventions
2.4
2.4. Analysis
Comparison 2: All‐cause mortality, Outcome 4: Subgroup analysis: all‐cause mortality ‐ level of FiO2/target in higher group
2.5
2.5. Analysis
Comparison 2: All‐cause mortality, Outcome 5: Subgroup analysis: all‐cause mortality ‐ level of FiO2/target in lower group
2.6
2.6. Analysis
Comparison 2: All‐cause mortality, Outcome 6: Subgroup analysis: all‐cause mortality ‐ ICU‐population
2.7
2.7. Analysis
Comparison 2: All‐cause mortality, Outcome 7: Subgroup analysis: all‐cause mortality ‐ oxygen delivery system
2.8
2.8. Analysis
Comparison 2: All‐cause mortality, Outcome 8: Sensitivity analysis: all‐cause mortality ‐ high vs high oxygenation strategies and low vs low oxygenation strategies excluded
2.9
2.9. Analysis
Comparison 2: All‐cause mortality, Outcome 9: Sensitivity analysis: all‐cause mortality ‐ best‐worst‐case scenario
2.10
2.10. Analysis
Comparison 2: All‐cause mortality, Outcome 10: Sensitivity analysis: all‐cause mortality ‐ worst‐best‐case scenario
3.1
3.1. Analysis
Comparison 3: Proportion of patients with one or more serious adverse events, Outcome 1: Highest proportion of specific serious adverse events reported
3.2
3.2. Analysis
Comparison 3: Proportion of patients with one or more serious adverse events, Outcome 2: Cumulated number of serious adverse events
3.3
3.3. Analysis
Comparison 3: Proportion of patients with one or more serious adverse events, Outcome 3: Proportion of patients with one or more serious adverse event (as defined by trialists)
4.1
4.1. Analysis
Comparison 4: Quality of life, Outcome 1: Quality of life
4.2
4.2. Analysis
Comparison 4: Quality of life, Outcome 2: Subgroup analysis: quality of life ‐ risk of bias
4.3
4.3. Analysis
Comparison 4: Quality of life, Outcome 3: Subgroup analysis: quality of life ‐ types of oxygen intervention
4.4
4.4. Analysis
Comparison 4: Quality of life, Outcome 4: Subgroup analysis: quality of life ‐ level of FiO2/target in higher group
4.5
4.5. Analysis
Comparison 4: Quality of life, Outcome 5: Subgroup analysis: quality of life ‐ level of FiO2/target in lower group
4.6
4.6. Analysis
Comparison 4: Quality of life, Outcome 6: Subgroup analysis: quality of life ‐ ICU‐population
4.7
4.7. Analysis
Comparison 4: Quality of life, Outcome 7: Subgroup analysis: quality of life ‐ oxygen delivery system
4.8
4.8. Analysis
Comparison 4: Quality of life, Outcome 8: Sensitivity analysis: quality of life ‐ best‐worst‐case scenario
4.9
4.9. Analysis
Comparison 4: Quality of life, Outcome 9: Sensitivity analysis: quality of life ‐ worst‐best‐case scenario
5.1
5.1. Analysis
Comparison 5: Lung injury, Outcome 1: Lung injury ‐ highest proportion reported
5.2
5.2. Analysis
Comparison 5: Lung injury, Outcome 2: Lung injury ‐ cumulated number
5.3
5.3. Analysis
Comparison 5: Lung injury, Outcome 3: Acute respiratory distress syndrome
5.4
5.4. Analysis
Comparison 5: Lung injury, Outcome 4: Pneumonia
6.1
6.1. Analysis
Comparison 6: Myocardial infartion, Outcome 1: Myocardial infarction
6.2
6.2. Analysis
Comparison 6: Myocardial infartion, Outcome 2: Subgroup analysis: myocardial infarction ‐ overall risk of bias
6.3
6.3. Analysis
Comparison 6: Myocardial infartion, Outcome 3: Subgroup analysis: myocardial infarction ‐ types of oxygen interventions
6.4
6.4. Analysis
Comparison 6: Myocardial infartion, Outcome 4: Subgroup analysis: myocardial infarction ‐ level of FiO2/target in higher group
6.5
6.5. Analysis
Comparison 6: Myocardial infartion, Outcome 5: Subgroup analysis: myocardial infarction ‐ level of FiO2/target in lower group
6.6
6.6. Analysis
Comparison 6: Myocardial infartion, Outcome 6: Subgroup analysis: myocardial infarction ‐ ICU‐population
6.7
6.7. Analysis
Comparison 6: Myocardial infartion, Outcome 7: Subgroup analysis: myocardial infarction ‐ oxygen delivery system
6.8
6.8. Analysis
Comparison 6: Myocardial infartion, Outcome 8: Sensitivity analysis: myocardial infarction ‐ best‐worst‐case scenario
6.9
6.9. Analysis
Comparison 6: Myocardial infartion, Outcome 9: Sensitivity analysis: myocardial infarction ‐ worst‐best‐case scenario
7.1
7.1. Analysis
Comparison 7: Stroke, Outcome 1: Stroke
7.2
7.2. Analysis
Comparison 7: Stroke, Outcome 2: Subgroup analysis: stroke ‐ overall risk of bias
7.3
7.3. Analysis
Comparison 7: Stroke, Outcome 3: Subgroup analysis: stroke ‐ types of oxygen interventions
7.4
7.4. Analysis
Comparison 7: Stroke, Outcome 4: Subgroup analysis: stroke ‐ level of FiO2/target in the higher group
7.5
7.5. Analysis
Comparison 7: Stroke, Outcome 5: Subgroup analysis: stroke ‐ level of FiO2/target in lower group
7.6
7.6. Analysis
Comparison 7: Stroke, Outcome 6: Subgroup analysis: stroke ‐ ICU‐population
7.7
7.7. Analysis
Comparison 7: Stroke, Outcome 7: Subgroup analysis: stroke ‐ oxygen delivery system
7.8
7.8. Analysis
Comparison 7: Stroke, Outcome 8: Sensitivity analysis: stroke ‐ high vs high oxygenation strategies and low vs low oxygenation strategies excluded
7.9
7.9. Analysis
Comparison 7: Stroke, Outcome 9: Sensitivity analysis: stroke ‐ best‐worst‐case scenario
7.10
7.10. Analysis
Comparison 7: Stroke, Outcome 10: Sensitivity analysis: stroke ‐ worst‐best‐case scenario
8.1
8.1. Analysis
Comparison 8: Sepsis, Outcome 1: Sepsis
8.2
8.2. Analysis
Comparison 8: Sepsis, Outcome 2: Subgroup analysis: sepsis ‐ overall risk of bias
8.3
8.3. Analysis
Comparison 8: Sepsis, Outcome 3: Subgroup analysis: sepsis ‐ types of oxygen interventions
8.4
8.4. Analysis
Comparison 8: Sepsis, Outcome 4: Subgroup analysis: sepsis ‐ level of FiO2/target in higher group
8.5
8.5. Analysis
Comparison 8: Sepsis, Outcome 5: Subgroup analysis: sepsis ‐ level of FiO2/target in lower group
8.6
8.6. Analysis
Comparison 8: Sepsis, Outcome 6: Subgroup analysis: sepsis ‐ ICU‐population
8.7
8.7. Analysis
Comparison 8: Sepsis, Outcome 7: Subgroup analysis: sepsis ‐ oxygen delivery system
8.8
8.8. Analysis
Comparison 8: Sepsis, Outcome 8: Sensitivity analysis: sepsis ‐ best‐worst‐case scenario
8.9
8.9. Analysis
Comparison 8: Sepsis, Outcome 9: Sensitivity analysis: sepsis ‐ worst‐best‐case scenario
9.1
9.1. Analysis
Comparison 9: Specific serious adverse events, Outcome 1: Myocardial infarction
9.2
9.2. Analysis
Comparison 9: Specific serious adverse events, Outcome 2: Stroke
9.3
9.3. Analysis
Comparison 9: Specific serious adverse events, Outcome 3: Sepsis
9.4
9.4. Analysis
Comparison 9: Specific serious adverse events, Outcome 4: Acute respiratory distress syndrome
9.5
9.5. Analysis
Comparison 9: Specific serious adverse events, Outcome 5: Pneumonia
9.6
9.6. Analysis
Comparison 9: Specific serious adverse events, Outcome 6: Delirium
9.7
9.7. Analysis
Comparison 9: Specific serious adverse events, Outcome 7: Pneumothorax
9.8
9.8. Analysis
Comparison 9: Specific serious adverse events, Outcome 8: Intestinal ischaemia
9.9
9.9. Analysis
Comparison 9: Specific serious adverse events, Outcome 9: Cardiovascular failure including shock
9.10
9.10. Analysis
Comparison 9: Specific serious adverse events, Outcome 10: Cardiac arrhythmia
9.11
9.11. Analysis
Comparison 9: Specific serious adverse events, Outcome 11: Liver failure
9.12
9.12. Analysis
Comparison 9: Specific serious adverse events, Outcome 12: Renal failure
9.13
9.13. Analysis
Comparison 9: Specific serious adverse events, Outcome 13: Seizure
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Update of

References

References to studies included in this review

Asfar 2017 {published data only}
    1. Asfar P, Schortgen F, Boisramé-Helms J, Charpentier J, Guérot E, Megarbane B, et al. Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respiratory Medicine 2017;5(3):180-90. [DOI: 10.1016/S2213-2600(17)30046-2] [PMID: ] - DOI - PubMed
Barrot 2020 {published data only}
    1. Barrot L, Asfar P, Mauny F, Winiszewski H, Montini F, Badie J, et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. New England Journal of Medicine 2020;382(11):999-1008. [DOI: 10.1056/NEJMoa1916431] [PMID: ] - DOI - PubMed
Gelissen 2021 {published data only}
    1. Gelissen H, Grooth HJ, Smulders Y, Wils E, Ruijter W, Vink R, et al. Effect of low-normal vs high-normal oxygenation targets on organ dysfunction in critically ill patients: a randomized clinical trial. Journal of American Medical Association 2021;326(10):940-8. [DOI: 10.1001/jama.2021.13011] [PMID: ] - DOI - PMC - PubMed
Girardis 2016 {published data only}
    1. Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. Journal of American Medical Association 2016;316(15):1583-9. [DOI: 10.1001/jama.2016.11993] [PMID: ] - DOI - PubMed
Gomersall 2002 {published data only}
    1. Gomersall CD, Joynt GM, Freebairn RC, Lai CK, Oh TE. Oxygen therapy for hypercapnic patients with chronic obstructive pulmonary disease and acute respiratory failure: a randomized, controlled pilot study. Critical Care Medicine 2002;30(1):113-6. [DOI: 10.1097/00003246-200201000-00018] [PMID: ] - DOI - PubMed
Ishii 2018 {published data only}
    1. Ishii K, Morimatsu H, Hyodo T, Ono K, Hidaka H, Koyama Y, et al. Relationship between inspired oxygen concentration and atelectasis formation after extubation. Critical Care Medicine 2018;46(1 Suppl 1):533. [DOI: 10.1097/01.ccm.0000529104.66235.9e] - DOI
Jakkula 2018 {published data only}
    1. Jakkula P, Reinikainen M, Hästbacka J, Loisa P, Tiainen M, Pettilä V, et al. Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Medicine 2018;44(12):2112-21. [DOI: 10.1007/s00134-018-5453-9] [PMID: ] - DOI - PMC - PubMed
Jun 2019 {published data only}
    1. Jun J, Sun L, Wang Y, Liu F, Yang G, Han B. Invasive mechanical ventilation with high concentration oxygen therapy for AECOPD patients with acute myocardial infarction. Chest 2019;156(4 Suppl):A958. [DOI: 10.1016/j.chest.2019.08.886] - DOI
Lång 2018 {published data only}
    1. Lång M, Skrifvars MB, Siironen J, Tanskanen P, Ala-Peijari M, Koivisto T, et al. A pilot study of hyperoxemia on neurological injury, inflammation and oxidative stress. Acta Anaesthesiologica Scandinavica 2018;62(6):801-10. [DOI: 10.1111/aas.13093] [PMID: ] - DOI - PubMed
Mackle 2020 {published data only}
    1. Mackle D, Bellomo R, Bailey M, Beasley R, Deane A, Eastwood G, et al, The ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Conservative oxygen therapy during mechanical ventilation in the ICU. New England Journal of Medicine 2020;382(11):989-98. [DOI: ] [PMID: ] - PubMed
Martin 2021 {published data only}
    1. Martin DS, McNeil M, Brew-Graves C, Filipe H, O’Driscoll R, Stevens JL, et al. A feasibility randomised controlled trial of targeted oxygen therapy in mechanically ventilated critically ill patients. Journal of the Intensive Care Society 2021;22(4):280-7. [DOI: 10.1177/17511437211010031] - DOI - PMC - PubMed
Mazdeh 2015 {published data only}
    1. Mazdeh M, Taher A, Torabian S, Seifirad S. Effects of normobaric hyperoxia in severe acute stroke: a randomized controlled clinical trial study. Acta Medica Iranica 2015;53(11):676-80. [PMID: ] - PubMed
Panwar 2016 {published data only}
    1. Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, et al. Conservative versus liberal oxygenation targets for mechanically ventilated patients – a pilot multicenter randomized controlled trial. American Journal of Respiratory and Critical Care Medicine 2016;193(1):43-51. [DOI: 10.1164/rccm.201505-1019OC] [PMID: ] - DOI - PubMed
Schjørring 2021 {published data only}
    1. Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, et al. Lower or higher oxygenation targets for acute hypoxemic respiratory failure. New England Journal of Medicine 2021;384(14):1301-11. [DOI: 10.1056/NEJMoa2032510] [PMID: ] - DOI - PubMed
Schmidt 2022 {published data only}
    1. Schmidt H, Kjaergaard J, Hassager C, Mølstrøm S, Grand J, Borregaard B, et al. Oxygen targets in comatose survivors of cardiac arrest. New England Journal of Medicine 2022;387(16):1467-76. [DOI: 10.1056/NEJMoa2208686] [PMID: ] - DOI - PubMed
Semler 2022 {published data only}
    1. Semler MW, Casey JD, Lloyd BD, Hastings PG, Hays MA, Stollings JL, et al. Oxygen-saturation targets for critically ill adults receiving mechanical ventilation. New England Journal of Medicine 2022;387(19):1759-69. [DOI: 10.1056/NEJMoa2208415 Abstract] [PMID: ] - PMC - PubMed
Taher 2016 {published data only}
    1. Taher A, Pilehvari Z, Poorolajal J, Aghajanloo M. Effects of normobaric hyperoxia in traumatic brain injury: a randomized controlled clinical trial. Trauma Monthly 2016;21(1):e26772. [DOI: 10.5812/traumamon.26772] [PMID: ] - DOI - PMC - PubMed
Yang 2019 {published data only}
    1. Yang X, Shang Y, YuanS. Low versus high pulse oxygen saturation directed oxygen therapy in critically ill patients: a randomized controlled pilot study. Journal of Thoracic Disease 2019;11(10):4234-40. [DOI: 10.21037/jtd.2019.09.66] - DOI - PMC - PubMed
Yang 2021 {published data only}
    1. Yang W, Zhang L. Observation of the curative effect of conservative oxygen therapy in mechanical ventilation of patients with severe pneumonia [保守氧疗法在重症肺炎机械通气患者中的应用效果观察]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021;33(9):1069-73. [DOI: 10.3760/cma.j.cn121430-20210617-00902] [PMID: ] - DOI - PubMed

References to studies excluded from this review

Ahimahalle 2019 {published data only}
    1. Ahimahalle TZ, Amirfarhangi A, Jabbari M, Jenabi A, Bagherzadegan H, Noghabaei G. Impact of oxygen therapy to ameliorate contrast-induced nephropathy in patients with acute coronary syndrome undergoing emergency angiography; a double-blinded clinical trial. Journal of Renal Injury Prevention 2019;8(4):283-8. [DOI: 10.15171/jrip.2019.52] - DOI
Ali 2013 {published data only}
    1. Ali K, Warusevitane A, Lally F, Sim J, Sills S, Pountain S, et al. The stroke oxygen pilot study: a randomized controlled trial of the effects of routine oxygen supplementation early after acute stroke – effect on key outcomes at six months. PLOS One 2013;8(6):e59274. [DOI: 10.1371/journal.pone.0059274] [PMID: ] - DOI - PMC - PubMed
Amar 1994 {published data only}
    1. Amar D, Greenberg MA, Menegus MA, Breitbart S. Should all patients undergoing cardiac catheterization or percutaneous transluminal coronary angioplasty receive oxygen? Chest 1994;105(3):727-32. [DOI: 10.1378/chest.105.3.727] [PMID: ] - DOI - PubMed
Austin 2010 {published data only}
    1. Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. British Medical Journal 2010;341:c5462. [DOI: 10.1136/bmj.c5462] [PMID: ] - DOI - PMC - PubMed
Baekgaard 2019 {published data only}
    1. Baekgaard JS, Isbye D, Ottosen CI, Larsen MH, Andersen JH, Rasmussen LS, et al. Restrictive vs liberal oxygen for trauma patients – the TRAUMOX1 pilot randomised clinical trial. Acta Anaesthesiol Scandinavica 2019;63(7):947-55. [DOI: 10.1111/aas.13362] [PMID: ] - DOI - PubMed
Bardsley 2018 {published data only}
    1. Bardsley G, Pilcher J, McKinstry S, Shirtcliffe P, Berry J, Fingleton J, et al. Oxygen versus air-driven nebulisers for exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial. BMC Pulmonary Medicine 2018;18(1):157. [DOI: 10.1186/s12890-018-0720-7] [PMID: ] - DOI - PMC - PubMed
Bickel 2011 {published data only}
    1. Bickel A, Gurevits M, Vamos R, Ivry S, Eitan A. Perioperative hyperoxygenation and wound site infection following surgery for acute appendicitis: a randomized, prospective, controlled trial. Archives of Surgery 2011;146(4):464-70. [DOI: 10.1001/archsurg.2011.65] [PMID: ] - DOI - PubMed
Bray 2018 {published data only}
    1. Bray JE, Hein C, Smith K, Stephenson M, Grantham H, Finn J. Oxygen titration after resuscitation from out-of-hospital cardiac arrest: a multi-centre, randomised controlled pilot study (the EXACT pilot trial). Resuscitation 2018;128:211-5. [DOI: 10.1016/j.resuscitation.2018.04.019] [PMID: ] - DOI - PubMed
Butler 1987 {published data only}
    1. Butler CM, Ham RO, Lafferty K, Cotton LT, Roberts VC. The effect of adjuvant oxygen therapy on transcutaneous pO2 and healing in the below-knee amputee. Prosthetics and Orthotics International 1987;11(1):10-16. [DOI: 10.3109/03093648709079373] [PMID: ] - DOI - PubMed
Cheng 2021 {published data only}
    1. Cheng Z, Geng X, Tong Y, Dornbos D, Hussain M, Rajah GB, et al. Adjuvant high-flow normobaric oxygen after mechanical thrombectomy for anterior circulation stroke: a randomized clinical trial. Neurotherapeutics 2021;18(2):188-97. [DOI: 10.1007/s13311-020-00979-3] [PMID: ] - DOI - PMC - PubMed
Heidari 2017 {published data only}
    1. Heidari F, Rahzani K, Iranpoor D, Rezaee K. The effect of oxygen on the outcomes of non-ST-segment elevation acute coronary syndromes. International Journal of Cardiology: Metabolic and Endocrine 2017;14:67-71. [DOI: 10.1016/j.ijcme.2016.12.002] - DOI
Hofmann 2017 {published data only}
    1. Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, et al, DETO2X–SWEDEHEART Investigators. Oxygen therapy in suspected acute myocardial infarction. New England Journal of Medicine 2017;377(13):1240-9. [DOI: 10.1056/NEJMoa1706222] [PMID: ] - DOI - PubMed
Huynh Ky 2017 {published data only}
    1. Huynh Ky M, Bouchard PA, Morin J, L'Her E, Sarrazin JF, Lellouche F. Closed-loop adjustment of oxygen flowrate with FreeO2 in patients with acute coronary syndrome: comparison of automated titration with FreeO2 (set at two SpO2 target) and of manual titration. A randomized controlled study. American Journal of Respiratory and Critical Care Medicine 2017;195:A3766.
Khoshnood 2017 {published data only}
    1. Khoshnood A, Akbarzadeh M, Roijer A, Meurling C, Carlsson M, Bhiladvala P, et al. Effects of oxygen therapy on wall-motion score index in patients with ST elevation myocardial infarction – the randomized SOCCER trial. Echocardiography 2017;34(8):1130-7. [DOI: 10.1111/echo.13599] [PMID: ] - DOI - PubMed
Khoshnood 2018 {published data only}
    1. Khoshnood A, Carlsson M, Akbarzadeh M, Bhiladvala P, Roijer A, Nordlund D, et al. Effect of oxygen therapy on myocardial salvage in ST elevation myocardial infarction: the randomized SOCCER trial. European Journal of Emergency Medicine 2018;25(2):78-84. [DOI: 10.1097/MEJ.0000000000000431] [PMID: ] - DOI - PubMed
Kuisma 2006 {published data only}
    1. Kuisma M, Boyd J, Voipio V, Alaspää A, Roine RO, Rosenberg P. Comparison of 30 and the 100% inspired oxygen concentrations during early post-resuscitation period: a randomised controlled pilot study. Resuscitation 2006;69(2):199-206. [DOI: 10.1016/j.resuscitation.2005.08.010] [PMID: ] - DOI - PubMed
Meyhoff 2009 {published data only}
    1. Meyhoff CS, Wetterslev J, Jorgensen LN, Henneberg SW, Høgdall C, Lundvall L, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. Journal of American Medical Association 2009;302(14):1543-50. [DOI: 10.1001/jama.2009.1452] [PMID: ] - DOI - PubMed
Mokhtari 2020 {published data only}
    1. Mokhtari A, Akbarzadeh M, Sparv D, Bhiladvala P, Arheden H, Erlinge D, et al. Oxygen therapy in patients with ST elevation myocardial infarction based on the culprit vessel: results from the randomized controlled SOCCER trial. BMC Emergency Medicine 2020;20(1):12. [DOI: 10.1186/s12873-020-00309-y] [PMID: ] - DOI - PMC - PubMed
Padma 2010 {published data only}
    1. Padma MV, Bhasin A, Bhatia R, Garg A, Singh MB, Tripathi M, et al. Normobaric oxygen therapy in acute ischemic stroke: a pilot study in Indian patients. Annals of Indian Academy of Neurology 2010;13(4):284-8. [DOI: 10.4103/0972-2327.74203] [PMID: ] - DOI - PMC - PubMed
Perrin 2011 {published data only}
    1. Perrin K, Wijesinghe M, Healy B, Wadsworth K, Bowditch R, Bibby S, et al. Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma. Thorax 2011;66(11):937-41. [DOI: 10.1136/thx.2010.155259] [PMID: ] - DOI - PubMed
Ranchord 2012 {published data only}
    1. Ranchord AM, Argyle R, Beynon R, Perrin K, Sharma V, Weatherall M, et al. High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomized controlled trial. American Heart Journal 2012;163(2):168-75. [DOI: 10.1016/j.ahj.2011.10.013] [PMID: ] - DOI - PubMed
Rawles 1976 {published data only}
    1. Rawles JM, Kenmure AC. Controlled trial of oxygen in uncomplicated myocardial infarction. British Medical Journal 1976;1(6018):1121-3. [DOI: 10.1136/bmj.1.6018.1121] [PMID: ] - DOI - PMC - PubMed
Rodrigo 2003 {published data only}
    1. Rodrigo GJ, Rodriquez Verde M, Peregalli V, Rodrigo C. Effects of short-term 28% and 100% oxygen on PaCO2 and peak expiratory flow rate in acute asthma: a randomized trial. Chest 2003;124(4):1312-7. [DOI: 10.1378/chest.124.4.1312] [PMID: ] - DOI - PubMed
Roffe 2010 {published data only}
    1. Roffe C, Sills S, Pountain SJ, Allen M. A randomized controlled trial of the effect of fixed-dose routine nocturnal oxygen supplementation on oxygen saturation in patients with acute stroke. Journal of Stroke and Cerebrovascular Diseases 2010;19(1):29-35. [DOI: 10.1016/j.jstrokecerebrovasdis.2009.02.008] [PMID: ] - DOI - PubMed
Roffe 2017 {published data only}
    1. Roffe C, Nevatte T, Sim J, Bishop J, Ives N, Ferdinand P, et al. Effect of routine low-dose oxygen supplementation on death and disability in adults with acute stroke: the stroke oxygen study randomized clinical trial. Journal of American Medical Association 2017;318(12):1125-35. [DOI: 10.1001/jama.2017.11463] [PMID: ] - DOI - PMC - PubMed
Sepehrvand 2019 {published data only}
    1. Sepehrvand N, Alemayehu W, Rowe BH, McAlister FA, Diepen S, Stickland M, et al. High vs. low oxygen therapy in patients with acute heart failure: HiLo-HF pilot trial. ESC Heart Failure 2019;6(4):667-77. [DOI: 10.1002/ehf2.12448] [PMID: ] - DOI - PMC - PubMed
Sills 2003 {published data only}
    1. Sills S, Halim M, Roffe C. A pilot study of routine nocturnal oxygen supplementation in patients with acute stroke. Age and Ageing 2003;32(Suppl 2):ii41.
Singhal 2005 {published data only}
    1. Singhal AB, Benner T, Roccatagliata L, Koroshetz WJ, Schaefer PW, Lo EH, et al. A pilot study of normobaric oxygen therapy in acute ischemic stroke. Stroke 2005;36(4):797-802. [DOI: 10.1161/01.STR.0000158914.66827.2e] [PMID: ] - DOI - PubMed
Singhal 2013 {published data only}
    1. Singhal A, on Behalf of Partners SPOTRIAS Investigators. A phase IIb clinical trial of normobaric oxygen therapy (NBO) in acute ischemic stroke (AIS) (S02.001). Neurology 2013;80(7 Suppl):S02.001.
Stub 2014 {published data only}
    1. Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, et al. Air versus oxygen in ST-segment-elevation myocardial infarction. Circulation 2015;131(24):2143-50. [DOI: 10.1161/CIRCULATIONAHA.114.014494] [PMID: ] - DOI - PubMed
Ukholkina 2005 {published data only}
    1. Ukholkina GB, Kostianov IIu, Kuchkina NV, Grendo EP, Gofman IaB. Effect of oxygenotherapy used in combination with reperfusion in patients with acute myocardial infarction. Kardiologiia 2005;45(5):59. [PMID: ] - PubMed
Wu 2014 {published data only}
    1. Wu J, Nevatte T, Roffe C. The stroke oxygen supplementation (S02S) study: comparison of postal and telephone responses of 12 months questionnaire follow up. International Journal of Stroke 2014;9(Suppl 4):37.
Young 2014 {published data only}
    1. Young P, Bailey M, Bellomo R, Bernard S, Dicker B, Freebairn R, et al. HyperOxic Therapy OR NormOxic Therapy after out-of-hospital cardiac arrest (HOT OR NOT): a randomised controlled feasibility trial. Resuscitation 2014;85(12):1686-91. [DOI: 10.1016/j.resuscitation.2014.09.011] [PMID: ] - DOI - PubMed
Young 2017 {published data only}
    1. Young PJ, Mackle DM, Bailey MJ, Beasley RW, Bennett VL, Deane AM, et al. Intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX): results of the pilot phase. Critical Care and Resuscitation 2017;19(4):344-54. [PMID: ] - PubMed
Zughaft 2013 {published data only}
    1. Zughaft D, Bhiladvala P, Van Dijkman A, Harnek J, Madsen Hardig B, Bjork J. The analgesic effect of oxygen during percutaneous coronary intervention (the OXYPAIN trial). Acute Cardiac Care 2013;15(3):63-8. [DOI: 10.3109/17482941.2013.822083] [PMID: ] - DOI - PubMed

References to ongoing studies

ACTRN12620000391976 {published data only}
    1. ACTRN12620000391976. The mega randomised registry trial comparing conservative vs. liberal oxygenation targets [A randomised, registry-embedded, single blinded clinical trial comparing conservative oxygen therapy to liberal oxygen therapy in mechanically ventilated adults in the intensive care unit]. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379432&isReview... (first received 10 March 2020).
ChiCTR‐INR‐17012800 {published data only}
    1. ChiCTR-INR-17012800. The effect of conservative oxygen therapy in the mechanical ventilation patients. chictr.org.cn/showproj.html?proj=21892 (first received 26 September 2017).
ChiCTR‐IOR‐17011717 {published data only}
    1. ChiCTR-IOR-17011717. Comparing the effects of conservative oxygen therapy vs conventional oxygen therapy on outcomes in critically ill patients [The effects of conservative oxygen therapy vs conventional oxygen therapy on outcomes in critically ill patients: a randomised controlled trial]. chictr.org.cn/showproj.html?proj=19990 (first received 21 June 2017).
CTRI/2020/12/029614 {published data only}
    1. CTRI/2020/12/029614. Liberal use of oxygen in early stage of COVID-19 patients [Early liberal oxygen therapy in COVID-19: an open-labeled randomised control trial]. ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=49680&EncHid=&am... (first received 2 November 2020).
ISRCTN13384956 {published data only}
    1. ISRCTN13384956. Intensive care unit randomised trial comparing two approaches to oxygen therapy (UK-ROX). isrctn.com/ISRCTN13384956 (first received 8 December 2020).
JPRN‐UMIN000046914 {published data only}
    1. JPRN-UMIN000046914. Early restricted oxygen therapy after resuscitation from cardiac arrest trial [Early restricted oxygen therapy after resuscitation from cardiac arrest trial – ER-OXYTRAC trial]. trialsearch.who.int/Trial2.aspx?TrialID=JPRN-UMIN000046914 (first received 14 February 2022).
NCT02999932 {published data only}
    1. NCT02999932. Pulse Oxygen Saturation (SpO2) Directed Oxygen Therapy (POSDOT) [Effect of low vs high peripheral oxygen saturation (SpO 2 ) directed oxygen therapy on mortality among critically ill patients]. clinicaltrials.gov/show/NCT02999932 (first received 14 December 2016).
NCT04144868 {published data only}
    1. NCT04144868. Safety and efficacy of NBO in acute intracerebral hemorrhage. clinicaltrials.gov/show/NCT04144868 (first received 30 December 2019).
NCT04198077 {published data only}
    1. NCT04198077. Conservative versus conventional oxygen administration in critically ill patients [Conservative vs conventional oxygen administration in critically ill patients: effects on ICU mortality. A multicentre randomized open label clinical trial]. clinicaltrials.gov/show/NCT04198077 (first received 10 December 2019).
NCT04425031 {published data only}
    1. NCT04425031. Handling oxygenation targets in COVID-19 (HOT-COVID) [Handling oxygenation targets in COVID-19 patients with acute hypoxaemic respiratory failure in the intensive care unit: a randomised clinical trial of a lower versus a higher oxygenation target]. clinicaltrials.gov/show/NCT04425031 (first received 5 June 2020).
NCT04824703 {published data only}
    1. NCT04824703. Comparative study between liberal and conservative oxygen therapy in mechanically ventilated intensive care patients. clinicaltrials.gov/show/NCT04824703 (first received 26 March 2021).
NCT05404373 {published data only}
    1. NCT05404373. Treatment duration on normobaric hyperoxia in acute ischemic stroke [The efficacy and safety of normobaric hyperoxia on treatment duration for acute ischemic stroke patients with endovascular treatment]. clinicaltrials.gov/show/NCT05404373 (first received 3 June 2022).
NL7185 {published data only}
    1. NL7185. Arterial oxygenation targets in intensive care patients [ICONIC study − conservative versus conventional oxygenation targets in intensive care patients: study protocol for a randomized clinical trial]. onderzoekmetmensen.nl/en/trial/19970 (first received 20 July 2018).

Additional references

AARC 2002
    1. Kallstrom TJ, American Association for Respiratory Care. AARC clinical practice guideline. Oxygen therapy for adults in the acute care facility – 2002 revision & update. Respiratory Care 2002;47(6):717-20. [PMID: ] - PubMed
ACTRN12613000505707
    1. ACTRN12613000505707. Feasibility and safety of conservative versus liberal oxygen targets in the mechanically ventilated patients [A multicenter pilot study to determine whether the conservative oxygenation strategy is as feasible and safe as liberal oxygenation strategy for the ICU patients requiring invasive mechanical ventilation]. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364185 (first received 5 May 2013).
ACTRN12615000957594
    1. ACTRN12615000957594. Evaluating the effects of two approaches to oxygen therapy in intensive care unit patients requiring life support (mechanical ventilation) [A multicentre, randomised, single-blinded clinical trial comparing the effect of conservative oxygen therapy with standard care on ventilator-free days in mechanically ventilated adults in the intensive care unit]. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261... (first received 15 August 2006).
Adhikari 2010
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ARDS Definition Task Force 2012
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Barbateskovic 2021a
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Brenner 2012
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