Table 1: Some recent clinical studies on the risks of hyperoxia after cardiac arrest or myocardial infarction, in traumatic brain injury, stroke, sepsis, and mixed ICU patients.

ReferencesStudy designHyperoxia measurementsMain finding

After cardiac arrest or myocardial infarction

Kilgannon et al. 2010 [11].Retrospective cohort study, 120 hospitals, 6326 patients (nontraumatic cardiac arrest)First PaO2 in the first 24 hours.
Hyperoxia: PaO2 ≥ 300 mmHg
Hyperoxia was associated with an increased hospital mortality compared with either hypoxia or normoxia (OR 1.8 [1.5–2.2])

Bellomo et al. 2011 [23]Retrospective cohort study, 125 ICUs, 12108 patients (nontraumatic cardiac arrest)Worst PaO2 in first 24 h.
Hyperoxia: PaO2 ≥ 300 mmHg
Normoxia: PaO2 60–300 mmHg
Hyperoxia group had a higher hospital mortality than normoxia (OR 1.2 [1.1–1.6])

Kilgannon et al. 2011 [24]Retrospective cohort study, 120 hospitals, 4459 patients (nontraumatic cardiac arrest)Highest PaO2 in the first 24 hoursA 100 mmHg increase in PaO2 was associated with a 24% increase in mortality risk (OR 1.24 [1.18 to 1.31])

Ranchord et al. 2012 [25]Pilot randomized controlled trial, single-centre, 136 patients with STEMIPatients randomized to receive high-concentration (6 L/min) or titrated oxygen (to achieve oxygen saturation 93%–96%) for 6 hours after presentationNo differences in number of deaths in the two groups (relative risk 0.5, 95% CI 0.05–5.4, )

Janz et al. 2012 [26]Retrospective analysis of a prospective cohort study, single-centre 170 patients (cardiac arrest treated with mild therapeutic hypothermia)Highest PaO2 in first 24 h.Increased hospital mortality for every 100 mmHg increase in PaO2 (OR 1.49 [1.03, 2.14])

Lee et al. 2014 [27]Retrospective cohort study, single-centre, 213 patients (cardiac arrest treated with therapeutic hypothermia)Average PaO2 between ROSC and the end of rewarming.
Hyperoxia: PaO2 > 157 mmHg
Normoxia: PaO2 117–135 mmHg
V-shaped association between PaO2 and poor neurologic outcome at hospital discharge (OR 6.47 [1.68, 24.91])

Stub et al. 2015 [14]Prospective, randomized, controlled trial, 9 hospitals, 441 patients with STEMIPatients with an SpO2 > 94% were randomized to receive 8 L/min of oxygen or no supplemental oxygen from arrival of paramedics until transfer to the cardiac care unitAn increased rate of recurrent myocardial infarction, an increase in the frequency of cardiac arrhythmias, and an increase in myocardial infarct size at 6 months on magnetic resonance imaging in the supplement group

Elmer et al. 2015 [12]Retrospective analysis of a high-resolution database, single-centre, 184 patients postcardiac arrestMean hourly exposure in first 24 h.
Normoxia: PaO2 60–100 mmHg; Moderate hyperoxia: PaO2 101–299 mmHg;
Severe hyperoxia: PaO2 300 mmHg
Severe hyperoxia was associated with decreased survival (OR 0.83 [0.69–0.99] per hour exposure); moderate hyperoxia was not associated with survival but with improved SOFA score 24 h (OR 0.92 [0.87–0.98])

Eastwood et al. 2016 [13]Retrospective before-after nested cohort study, single-centre, 50 patients postcardiac arrestConservative oxygenation: SpO2 88–92%Conservative group had a shorter ICU length of stay; no difference in the proportion of survivors discharged from hospital with good neurological outcome compared to conventional group

In traumatic brain injury (TBI) and stroke

Davis et al. 2009 [18]Retrospective cohort study, 5 trauma centres, 3420 moderate-to-severe patientsExtreme hyperoxia: first PaO2 > 487 mmHgA PaO2 value of 110–487 mmHg was considered optimal. Extreme hyperoxia had an independent association with decreased survival (OR 0.50 [0.36, 0.71]) compared to optimal range

Brenner et al. 2012 [19]Retrospective study, single-centre, 1547 severe TBI patientsMean PaO2 in first 24 h hospital admission:
Hyperoxia: PaO2 > 200 mmHg
Normoxia: PaO2 100–200 mmHg
Both low and high PaO2 had increased mortality.
Patients with hyperoxia had higher hospital mortality (OR 1.50 [1.15–1.97]) and lower discharge GCS scores at discharge (OR 1.52 [1.18–1.96])

Raj et al. 2013 [20]Retrospective nested cohort analysis, 5 hospitals, 1116 ventilated moderate-to-severe TBI patientsWorst PaO2 in first 24 h ICU admission:
Hyperoxia: PaO2 > 100 mmHg
Normoxia: PaO2 75–100 mmHg
Hyperoxia had no independent relationship with in-hospital mortality (OR 0.94 [0.65–1.36]) and 6-month mortality (OR 0.88 [0.63–1.22])

Rincon et al. 2014 [28]Retrospective cohort, 84 ICUs, 2894 stroke patientsPaO2 in the first 24 hours.
Hyperoxia: PaO2 ≥ 300 mmHg
Normoxia: PaO2 60–300 mmHg
Hyperoxia was independently associated with in-hospital mortality (OR 1.22 [1.04–1.48])

Rincon et al. 2014 [29]Retrospective cohort study, 61 hospitals, 1212 ventilated TBI patientsHyperoxia: PaO2 > 300 mmHg
Normoxia: PaO2 60–300 mmHg
Hyperoxia was associated with a higher in-hosptial case fatality (OR 1.5 [1.02–2.4])

Jeon et al. 2014 [30]Prospective, observational cohort database analysis, single-centre, 252 patients (subarachnoid haemorrhage)PaO2 AUC by observation time until delayed cerebral ischemia (DCI). Hyperoxia: PaO2 ≥ 173 mmHg (upper quartile)Hyperoxia group had a higher incidence of DCI (OR 3.16 [1.69 to 5.92]) and poor outcome (modified Rankin Scale 4–6 at 3 months after subarachnoid haemorrhage) (OR 2.30 [1.03 to 5.12])

Quintard et al. 2015 [17]Retrospective analysis of a database, single-centre, 36 severe TBI patientsHyperoxia: PaO2 > 150 mmHgHyperoxia was associated with increased cerebral microdialysis glutamate, indicating cerebral excitotoxicity

Lang et al. 2016 [31]Retrospective analysis using 2 databases, 432 ventilated patients (subarachnoid haemorrhage)Time-weighted average PaO2 during the first 24 hours
Low PaO2 < 97.5 mmHg;
Intermediate PaO2 97.5–150 mmHg;
High PaO2 >150 mmHg
Patients with an unfavorable outcome had significantly higher PaO2, but high PaO2 has no effect on 3-month neurological outcomes (OR 1.09 [0.61–1.97]) or mortality (OR 0.73 [0.38–1.40])

In sepsis

Stolmeijer et al. 2014 [32]Prospective pilot study, 83 sepsis patients in emergency department, single-centrePaO2 after 5 min of a VentiMask 40% with 10 L O2/min.
Hyperoxia: PaO2 > 100 mmHg
Of the hyperoxic patients, 8% died in hospital versus 6% with normoxia

In mixed ICU patients

de Jonge et al. 2008 [4]Retrospective observational study, 50 ICUs, 36307 ventilated patientsWorst PaO2 in first 24 h.
Hyperoxia: PaO2 ≥ 123 mmHg (upper quintile) compared with PaO2 between 67 and 80 mmHg
In-hospital mortality was linearly related to FiO2 value and had a U-shaped relationship with PaO2. Hyperoxia had a higher mortality (OR 1.23 [1.13–1.34])

Panwar et al. 2016 [33]Pilot randomized controlled trial, 4 ICUs, 103 patientsConservative oxygenation: SpO2 88–92%
Liberal oxygenation: SpO2 ≥ 96%
No significant differences in measures of new organ dysfunction, or ICU or 90-day mortality (OR 0.77 [0.40–1.50])

Girardis et al. 2016 [34]Open-label randomized trial, single-centre, 434 patientsConservative oxygenation: PaO2 70–100 mmHg (SpO2 94–98%)
Conventional oxygenation: PaO2 > 150 mmHg (SpO2 97–100%)
Patients in the conservative group had lower ICU mortality (RR 0.57 [0.37–0.9]) and fewer episodes of shock, liver failure, and bacteraemia

Helmerhorst et al. 2017 [35]Observational cohort study, 3 ICUs, 14441 ventilated patientsFirst PaO2 at ICU admission
Mild hyperoxia: PaO2 120–200 mmHg
Severe hyperoxia: PaO2 > 200 mmHg
Severe hyperoxia was associated with higher mortality rates and fewer ventilator-free days in comparison to both mild hyperoxia and normoxia
Time spent in hyperoxia had a linear and positive relationship with hospital mortality

OR: odds ratio; SOFA: sequential organ failure assessment; ROSC: return of spontaneous circulation; DIC: delayed cerebral ischemia; AUC: area under the curve; STEMI: ST-segment elevated myocardial infarction.