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Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX)

  • Paul YoungEmail author
  • Diane Mackle
  • Rinaldo Bellomo
  • Michael Bailey
  • Richard Beasley
  • Adam Deane
  • Glenn Eastwood
  • Simon Finfer
  • Ross Freebairn
  • Victoria King
  • Natalie Linke
  • Edward Litton
  • Colin McArthur
  • Shay McGuinness
  • Rakshit Panwar
  • the ICU-ROX Investigators the Australian New Zealand Intensive Care Society Clinical Trials Group
Original

Abstract

Purpose

Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis.

Methods

We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU.

Results

Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO2 ≥ 97% (23.5 h [interquartile range (IQR) 8–70] vs. 47 h [IQR 11–93], absolute difference, 23 h; 95% CI 8–38), and more time receiving an FiO2 of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1–79] vs. 0 h [IQR 0–10], absolute difference, 20 h; 95% CI 14–26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI − 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy.

Conclusions

Point estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group.

Clinical Trials Registry

ICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594.

Keywords

Sepsis Septic shock Oxygen therapy Hyperoxia Hyperoxaemia Randomised controlled trials Intensive care 

Notes

Funding

Funded by the New Zealand Health Research Council (Grant No. >16-014).

Compliance with ethical standards

Conflicts of interest

The authors report no conflicts of interest.

Supplementary material

134_2019_5857_MOESM1_ESM.doc (218 kb)
Supplementary material 1 (DOC 217 kb)
134_2019_5857_MOESM2_ESM.docx (88 kb)
Supplementary material 2 (DOCX 88 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Paul Young
    • 1
    • 2
    Email author
  • Diane Mackle
    • 1
  • Rinaldo Bellomo
    • 3
    • 4
    • 5
    • 6
  • Michael Bailey
    • 3
    • 5
  • Richard Beasley
    • 1
  • Adam Deane
    • 5
    • 6
  • Glenn Eastwood
    • 3
    • 4
  • Simon Finfer
    • 7
    • 8
  • Ross Freebairn
    • 9
  • Victoria King
    • 3
  • Natalie Linke
    • 3
  • Edward Litton
    • 10
  • Colin McArthur
    • 1
    • 11
  • Shay McGuinness
    • 1
    • 12
  • Rakshit Panwar
    • 13
    • 14
  • the ICU-ROX Investigators the Australian New Zealand Intensive Care Society Clinical Trials Group
  1. 1.Medical Research Institute of New ZealandWellingtonNew Zealand
  2. 2.Intensive Care UnitWellington Regional HospitalWellington SouthNew Zealand
  3. 3.Australian and New Zealand Intensive Care Research CentreMonash UniversityMelbourneAustralia
  4. 4.Intensive Care UnitAustin HospitalHeidelbergAustralia
  5. 5.University of MelbourneParkvilleAustralia
  6. 6.Intensive Care UnitRoyal Melbourne HospitalParkvilleAustralia
  7. 7.Division of Critical Care and TraumaThe George Institute for Global HealthSydneyAustralia
  8. 8.Malcolm Fisher Department of Intensive Care MedicineRoyal North Shore HospitalSt LeonardsAustralia
  9. 9.Intensive Care UnitHawkes Bay HospitalHastingsNew Zealand
  10. 10.Intensive Care UnitFiona Stanley HospitalMurdochAustralia
  11. 11.Department of Critical Care MedicineAuckland City HospitalAucklandNew Zealand
  12. 12.Cardiothoracic and Vascular Intensive Care UnitAuckland City HospitalAucklandNew Zealand
  13. 13.Intensive Care UnitJohn Hunter HospitalNew Lambton HeightsAustralia
  14. 14.School of Medicine and Public HealthUniversity of NewcastleNewcastleAustralia

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