BACKGROUND: Trauma poses a significant global health challenge. Despite advancements in the management of severely injured patients, (poly)trauma continues to be a primary contributor to morbidity and mortality worldwide. In the context of trauma resuscitation, supplemental oxygen is commonly administered generously as suggested by guidelines. Yet, it remains uncertain whether the trauma population might derive advantages from a more conservative approach to supplemental oxygen.
METHODS: In this retrospective cohort study from two Swiss trauma centers, severely injured adult (> 16 years) trauma patients with an Injury Severity Score (ISS) ≥ 16 were divided into four groups according to the first blood gas analysis taken: hypoxaemia (PaO2 < 10.7 kPa/80 mmHg), normoxaemia (PaO2 10.7-16.0 kPa/80-120 mmHg), which served as reference, moderate hyperoxaemia (PaO2 > 16.0-40 kPa/120-300 mmHg) and severe hyperoxaemia (PaO2 > 40 kPa/300 mmHg). The primary outcome was 28-day mortality. Length of hospital stay (LOS) and length of intensive care unit stay (LOS-ICU) were analyzed as secondary outcomes.
RESULTS: Of 1,189 trauma patients, 41.3% had hyperoxaemia (18.8% with severe hyperoxaemia) and 19.3% had hypoxaemia. No difference was found for 28-day mortality (hypoxaemia: 15.7%, normoxaemia: 14.1%, hyperoxaemia: 13.8%, severe hyperoxaemia: 16.0%, p = 0.846). Patients with severe hyperoxaemia had a significant prolonged LOS (median 12.5 [IQR 7-18.5] days vs. 10 [7-17], p = 0.040) and extended LOS-ICU (3.8 [1.8-9] vs. 2 [1-5] days, p = 0.149) compared to normoxaemic patients. In multivariable analysis, oxygen group was not associated with the primary outcome 28-day mortality or LOS-ICU. Severe hyperoxaemia patients had a tendency towards longer hospital stay (adjusted coefficient 2.23 days [95% CI: - 0.32; 4.79], p = 0.087).
CONCLUSIONS: Hyperoxaemia was not associated with an increased 28-day mortality when compared to normoxaemia. However, both moderate and severe hyperoxaemia is frequently observed in trauma patients, and the presence of severe hyperoxaemia showed a tendency with extended hospital stay compared to normoxaemia patients. Robust randomized controlled trials are imperative to thoroughly evaluate the potential correlation between hyperoxaemia and outcomes in trauma patients . Trial Registration Retrospectively registered.

OBJECTIVE: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) frequently develop arterial hyperoxaemia, which may be harmful. However, lower oxygen saturation targets may also lead to harmful episodes of hypoxaemia.
METHODS: In this registry-embedded, multicentre trial, we randomly assigned adult patients receiving VA-ECMO in an intensive care unit (ICU) to either a conservative (target SaO2 92-96%) or to a liberal oxygen strategy (target SaO2 97-100%) through controlled oxygen administration via the ventilator and ECMO gas blender. The primary outcome was the number of ICU-free days to day 28. Secondary outcomes included ICU-free days to day 60, mortality, ECMO and ventilation duration, ICU and hospital lengths of stay, and functional outcomes at 6 months.
RESULTS: From September 2019 through June 2023, 934 patients who received VA-ECMO were reported to the EXCEL registry, of whom 300 (192 cardiogenic shock, 108 refractory cardiac arrest) were recruited. We randomised 149 to a conservative and 151 to a liberal oxygen strategy. The median number of ICU-free days to day 28 was similar in both groups (conservative: 0 days [interquartile range (IQR) 0-13.7] versus liberal: 0 days [IQR 0-13.7], median treatment effect: 0 days [95% confidence interval (CI) - 3.1 to 3.1]). Mortality at day 28 (59/159 [39.6%] vs 59/151 [39.1%]) and at day 60 (64/149 [43%] vs 62/151 [41.1%] were similar in conservative and liberal groups, as were all other secondary outcomes and adverse events. The conservative group experienced 44 (29.5%) major protocol deviations compared to 2 (1.3%) in the liberal oxygen group (P < 0.001).
CONCLUSIONS: In adults receiving VA-ECMO in ICU, a conservative compared to a liberal oxygen strategy, did not affect the number of ICU-free days to day 28.

BACKGROUND: The oxygen reserve index (ORi) is a real-time, continuous index measured with multi-wavelength pulse CO-oximetry technology. It estimates mild hyperoxemia in humans, which is defined as a partial pressure of oxygen (PaO2) level between 100 and 200 mmHg. The objectives of this study were to assess the correlation between ORi and PaO2, as well as to determine its ability in detecting mild hyperoxemia in dogs.
METHODS: This prospective observational study enrolled 37 anaesthetised and mechanically ventilated dogs undergoing elective procedures. Simultaneous measurements of ORi and PaO2 were collected, using a multi-wavelength pulse CO-oximeter with a probe placed on the dog\'s tongue, and a blood gas analyser, respectively. A mixed-effects model was used to calculate the correlation (r2) between simultaneous measurements of ORi and PaO2. The trending ability of ORi to identify dependable and proportional changes of PaO2 was determined. The diagnostic performances of ORi to detect PaO2 ≥ 150 mmHg and ≥ 190 mmHg were estimated using the area under the receiver operating characteristic curve (AUROC). The effects of perfusion index (PI), haemoglobin (Hb), arterial blood pH and partial pressure of carbon dioxide (PaCO2) on AUROC for PaO2 ≥ 150 mmHg were evaluated.
RESULTS: A total of 101 paired measurements of ORi and PaO2 were collected. PaO2 values ranged from 74 to 258 mmHg. A strong positive correlation (r2 = 0.52, p < 0.001) was found between ORi and PaO2. The trending ability ORi was 90.7%, with 92% sensitivity and 89% specificity in detecting decreasing PaO2. An ORi value ≥ 0.53 and ≥ 0.76 indicated a PaO2 ≥ 150 and ≥ 190 mmHg, respectively, with ≥ 82% sensitivity, ≥ 77% specificity and AUROC ≥ 0.75. The AUROC of ORi was not affected by PI, Hb, pH and PaCO2.
CONCLUSIONS: In anaesthetised dogs, ORi may detect mild hyperoxaemia, although it does not replace blood gas analysis for measuring the arterial partial pressure of oxygen. ORi monitoring could be used to non-invasively assess oxygenation in dogs receiving supplemental oxygen, limiting excessive hyperoxia.

UNASSIGNED: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain.
UNASSIGNED: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial.
UNASSIGNED: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU.
UNASSIGNED: The primary outcome is in-hospital all-cause mortality up to 90 d from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home.
UNASSIGNED: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias.
UNASSIGNED: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).

UNASSIGNED: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis receiving unplanned invasive mechanical ventilation in the intensive care unit (ICU) is uncertain.
UNASSIGNED: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial.
UNASSIGNED: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial.
UNASSIGNED: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of patients discharged home.
UNASSIGNED: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias.

BACKGROUND: Ventilated infants frequently require supplemental oxygen, but its use should be monitored carefully due to associated complications. The achievement of oxygen saturation (SpO2) targets can be challenging as neonates experience frequent fluctuations of their oxygen levels that further increase the risk of complications. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets, reduce hyperoxaemic episodes and facilitate weaning of the inspired oxygen concentration in ventilated infants born at or near term. This study investigates whether CLAC compared with manual oxygen control reduces the time spent in hyperoxia and the overall duration of supplemental oxygen treatment in ventilated infants born at or above 34 weeks gestation.
METHODS: This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 40 infants born at or above 34 weeks of gestation and within 24 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment till successful extubation. The primary outcome is the percentage of time spent in hyperoxia (SpO2 > 96%). The secondary outcomes are the overall duration of supplementary oxygen treatment, the percentage of time spent with an oxygen requirement above thirty per cent, the number of days on mechanical ventilation and the length of neonatal unit stay. The study is performed following informed parental consent and was approved by the West Midlands-Edgbaston Research Ethics Committee (Protocol version 1.2, 10/11/2022).
CONCLUSIONS: This trial will investigate the effect of CLAC on the overall duration of oxygen therapy and the time spent in hyperoxia. These are important clinical outcomes as hyperoxic injury is related to oxidative stress that can adversely affect multiple organ systems.
BACKGROUND: ClinicalTrials.Gov NCT05657795. Registered on 12/12/2022.

Oxygen (O2) toxicity remains a concern, particularly to the lung. This is mainly related to excessive production of reactive oxygen species (ROS). Supplemental O2, i.e. inspiratory O2 concentrations (FIO2) > 0.21 may cause hyperoxaemia (i.e. arterial (a) PO2 > 100 mmHg) and, subsequently, hyperoxia (increased tissue O2 concentration), thereby enhancing ROS formation. Here, we review the pathophysiology of O2 toxicity and the potential harms of supplemental O2 in various ICU conditions. The current evidence base suggests that PaO2 > 300 mmHg (40 kPa) should be avoided, but it remains uncertain whether there is an \"optimal level\" which may vary for given clinical conditions. Since even moderately supra-physiological PaO2 may be associated with deleterious side effects, it seems advisable at present to titrate O2 to maintain PaO2 within the normal range, avoiding both hypoxaemia and excess hyperoxaemia.

BACKGROUND: Oxygen therapy is routinely administered to mechanically ventilated patients. However, there remains uncertainty about the optimal oxygen titration target in patients with the acute respiratory distress syndrome (ARDS).
METHODS: Prospectively identified adult patients meeting the Berlin definition of ARDS between 1st January 2014 and 13th December 2016 were analyzed. Oxygen exposure variables were collected at 6-hourly intervals. The primary exposure was the average time-weighted partial pressure of arterial oxygen (PaO2) calculated over a maximum of 7 days from meeting ARDS criteria. The primary outcome was ICU mortality. Univariable and multivariable logistic regression analyses were performed to assess the impact of exposure variables on clinical outcomes. Results are presented as odds ratio [95% confidence interval].
RESULTS: 202 patients were included in the final analysis. Overall ICU mortality was 31%. The average time-weighted PaO2 during the first 7 days of ARDS was similar between non-survivors and survivors (11.3 kPa [10.2, 12.5] (84.8 mmHg [76.5, 93.8]) vs. 11.9 kPa [10.9, 12.6] (89.3 mmHg [81.8, 94.5]); p = 0.08). In univariable and multivariable analysis, average time-weighted PaO2 demonstrated a U-shaped relationship with ICU mortality. There was a similar relationship identified with hospital mortality.
CONCLUSIONS: In patients with ARDS, the predicted probability of both ICU and hospital mortality was lowest when the average time-weighted PaO2 was between 12.5 and 14 kPa (93.8-105.0 mmHg), suggesting this is a reasonable oxygenation target for clinicians to aim for.

Nearly all patients receiving treatment in a peri-operative or intensive care setting receive supplemental oxygen therapy. It is biologically plausible that the dose of oxygen used might affect important patient outcomes. Most peri-operative research has focussed on oxygen regimens that target higher than normal blood oxygen levels. Whereas, intensive care research has mostly focussed on conservative oxygen regimens which assiduously avoid exposure to higher than normal blood oxygen levels. While such conservative oxygen therapy is preferred for spontaneously breathing patients with chronic obstructive pulmonary disease, the optimal oxygen regimen in other patient groups is not clear. Some data suggest that conservative oxygen therapy might be preferred for patients with hypoxic ischaemic encephalopathy. However, unless oxygen supplies are constrained, routinely aggressively down-titrating oxygen in either the peri-operative or intensive care setting is not necessary based on available data. Targeting higher than normal levels of oxygen might reduce surgical site infections in the perioperative setting and/or improve outcomes for intensive care patients with sepsis but further research is required and available data are not sufficiently strong to warrant routine implementation of such oxygen strategies.

Multiple studies among adults have suggested a non-linear relationship between arterial partial pressure of oxygen (PaO2) and clinical outcomes. Meta-analyses in this population suggest that high levels of supplemental oxygen resulting in hyperoxia are associated with mortality. This mini-review focuses on the non-neonatal pediatric literature examining the relationship between PaO2 and mortality. While only one pilot pediatric randomized-controlled trials exists, over the past decade, there have been at least eleven observational studies examining the relationship between PaO2 values and mortality in critically ill children. These analyses of mixed-case pediatric ICU populations have generally reported a parabolic (\"u-shaped\") relationship between PaO2 and mortality, similar to that seen in the adult literature. However, the estimates of the point at which hyperoxemia becomes deleterious have varied widely (300-550 mmHg). Where attempted, this effect has been robust to analyses restricted to the first PaO2 value obtained, those obtained within 24 h of admission, anytime during admission, and the number of hyperoxemic blood gases over time. These findings have also been noted when using various methods of risk-adjustment (accounting for severity of illness scores or complex chronic conditions). Similar relationships were found in the majority of studies restricted to patients undergoing care after cardiac arrest. Taken together, the majority of the literature suggests that there is a robust parabolic relationship between PaO2 and risk-adjusted pediatric ICU mortality, but that the exact threshold at which hyperoxemia becomes deleterious is unclear, and likely beyond the typical target value for most clinical indications. Findings suggest that clinicians should remain judicious and thoughtful in the use of supplemental oxygen therapy in critically ill children.