Higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit: a Cochrane Review
Abstract
Background: The mainstay treatment for hypoxaemia is oxygen therapy, which is given to the vast majority of adults admitted to the intensive care unit (ICU). The practice of oxygen administration has been liberal, which may result in hyperoxaemia. Some studies have indicated an association between hyperoxaemia and mortality, whilst other studies have not. The ideal target for supplemental oxygen for adults admitted to the ICU is uncertain. Despite a lack of robust evidence of effectiveness, oxygen administration is widely recommended in international clinical practice guidelines. The potential benefit of supplemental oxygen must be weighed against the potentially harmful effects of hyperoxaemia.
Objectives: To assess the benefits and harms of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU.
Search methods
We identified trials through electronic searches of CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, BIOSIS Previews, CINAHL, and LILACS. We searched for ongoing or unpublished trials in clinical trials registers. We also scanned the reference lists of included studies. We ran the searches in December 2018.
Selection criteria: We included randomized controlled trials (RCTs) that compared higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU. We included trials irrespective of publication type, publication status, and language.
We included trials with a difference between the intervention and control groups of a minimum 1 kPa in partial pressure of arterial oxygen (PaO2), minimum 10% in fraction of inspired oxygen (FiO2), or minimum 2% in arterial oxygen saturation of haemoglobin/non‐invasive peripheral oxygen saturation (SaO2/SpO2).
We excluded trials randomizing participants to hypoxaemia (FiO2 below 0.21, SaO2/SpO2 below 80%, and PaO2 below 6 kPa) and to hyperbaric oxygen.
Data collection and analysis: Three review authors independently, and in pairs, screened the references retrieved in the literature searches and extracted data. Our primary outcomes were all‐cause mortality, the proportion of participants with one or more serious adverse events, and quality of life. None of the trials reported the proportion of participants with one or more serious adverse events according to the International Conference on Harmonisation Good Clinical Practice (ICH‐GCP) criteria. Nonetheless, most trials reported several serious adverse events. We therefore included an analysis of the effect of higher versus lower fraction of inspired oxygen, or targets using the highest reported proportion of participants with a serious adverse event in each trial. Our secondary outcomes were lung injury, acute myocardial infarction, stroke, and sepsis.
None of the trials reported on lung injury as a composite outcome, however some trials reported on acute respiratory distress syndrome (ARDS) and pneumonia. We included an analysis of the effect of higher versus lower fraction of inspired oxygen or targets using the highest reported proportion of participants with ARDS or pneumonia in each trial. To assess the risk of systematic errors, we evaluated the risk of bias of the included trials. We used GRADE to assess the overall certainty of the evidence.
Main results: We included 10 RCTs (1458 participants), seven of which reported relevant outcomes for this review (1285 participants). All included trials had an overall high risk of bias, whilst two trials had a low risk of bias for all domains except blinding of participants and personnel.
Meta‐analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding mortality at the time point closest to three months (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.01 to 1.37; I2 = 0%; 4 trials; 1135 participants; very low‐certainty evidence). Meta‐analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding serious adverse events at the time point closest to three months (estimated highest proportion of specific serious adverse events in each trial RR 1.13, 95% CI 1.04 to 1.23; I2 = 0%; 1234 participants; 6 trials; very low‐certainty evidence). These findings should be interpreted with caution given that they are based on very low‐certainty evidence.
None of the included trials reported any data on quality of life at any time point.
Meta‐analysis indicated no evidence of a difference between higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation on lung injury at the time point closest to three months (estimated highest reported proportion of lung injury RR 1.03, 95% CI 0.78 to 1.36; I2 = 0%; 1167 participants; 5 trials; very low‐certainty evidence).
None of the included trials reported any data on acute myocardial infarction or stroke, and only one trial reported data on the effects on sepsis.
Authors' conclusions: We are very uncertain about the effects of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU on all‐cause mortality, serious adverse events, and lung injuries at the time point closest to three months due to very low‐certainty evidence. Our results indicate that oxygen supplementation with higher versus lower fractions or oxygenation targets may increase mortality. None of the trials reported the proportion of participants with one or more serious adverse events according to the ICH‐GCP criteria, however we found that the trials reported an increase in the number of serious adverse events with higher fractions or oxygenation targets. The effects on quality of life, acute myocardial infarction, stroke, and sepsis are unknown due to insufficient data.
References
References to studies included in this review:
Asfar 2017 {published data only}
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. [PUBMED: 28219612]
Girardis 2016 {published data only}
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. JAMA 2016;316(15):1583‐9. [PUBMED: 27706466]
Gomersall 2002 {published data only}
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. [PUBMED: 11905405]
Ishii 2018 {published data only}
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]
Jakkula 2018 {published data only}
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. [PUBMED: 30430209]
Lång 2018 {published data only}
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. [PUBMED: 29464691]
Mazdeh 2015 {published data only}
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. [PUBMED: 26786987]
Panwar 2016 {published data only}
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. [PUBMED: 26334785]
Taher 2016 {published data only}
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. [PUBMED: 27218057]
Young 2017 {published data only}
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. [PUBMED: 29202261]
References to studies excluded from this review:
Ali 2013 {published data only}
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. [PUBMED: 23755093]
Amar 1994 {published data only}
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. [PUBMED: 8131533]
Austin 2010 {published data only}
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. BMJ 2010;341:c5462. [PUBMED: 20959284]
Bickel 2011 {published data only}
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. [PUBMED: 21502457]
Bray 2018 {published data only}
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. [PUBMED: 29684433]
Hofmann 2017 {published data only}
Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, et al. Oxygen therapy in suspected acute myocardial infarction. New England Journal of Medicine 2017;377(13):1240‐9. [PUBMED: 28844200]
Huynh Ky 2017 {published data only}
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. Annals of Intensive Care 2017;7(Suppl 1):O59.
Khoshnood 2018 {published data only}
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. [PUBMED: 27893526]
Khosnood 2017 {published data only}
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. [PUBMED: 28664557]
Kuisma 2006 {published data only}
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. [PUBMED: 16500018]
Meyhoff 2009 {published data only}
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. JAMA 2009;302(14):1543‐50. [PUBMED: 19826023]
Padma 2010 {published data only}
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. [PUBMED: 21264137]
Perrin 2011 {published data only}
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. [PUBMED: 21597111]
Ranchord 2012 {published data only}
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. [PUBMED: 22305833]
Rawles 1976 {published data only}
Rawles JM, Kenmure AC. Controlled trial of oxygen in uncomplicated myocardial infarction. BMJ 1976;1(6018):1121‐3. [PUBMED: 773507]
Rodrigo 2003 {published data only}
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. [PUBMED: 14555560]
Roffe 2010 {published data only}
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. [PUBMED: 20123224]
Roffe 2017 {published data only}
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. JAMA 2017;318(12):1125‐35. [PUBMED: 28973619]
Sills 2003 {published data only}
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}
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. [PUBMED: 15761201]
Singhal 2013 {published data only}
Singhal A. A phase IIb clinical trial of normobaric oxygen therapy (NBO) in acute ischemic stroke (AIS). Neurology 2013;80(Suppl 7):S02.001.
Stub 2014 {published data only}
Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, et al. Air versus oxygen in S‐segment‐elevation myocardial infarction. Circulation 2015;131(24):2143‐50. [PUBMED: 26002889]
Ukholkina 2005 {published data only}
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. [PUBMED: 16007057]
Wu 2014 {published data only}
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}
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. [PUBMED: 25261605]
Zughaft 2013 {published data only}
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. [PUBMED: 23957447]
References to studies awaiting assessment:
ICU‐ROX 2019 {published data only}
ICU‐ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group, Mackle D, Bellomo R, Bailey M, Beasley R, Deane A, Eastwood G, Finfer S, Freebairn R, King V, Linke N, Litton E, McArthur C, McGuinness S, Panwar R, Young P. Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. New England Journal of Medicine 2019:[Epub ahead of print]. [PUBMED: 31613432]
References to ongoing studies:
NCT02321072 {published data only}
NCT02321072. Optimal oxygenation in the intensive care unit (O2‐ICU). clinicaltrials.gov/ct2/show/NCT02321072 (first received 9 December 2014).
NCT02713451 {published data only}
NCT02713451. Liberal oxygenation versus conservative oxygenation in ARDS (LOCO2). clinicaltrials.gov/ct2/show/NCT02713451 (first received 18 March 2016).
NCT03141099 {published data only}
NCT03141099. Blood pressure and OXygenation targets after OHCA (BOX). clinicaltrials.gov/ct2/show/NCT03141099 (first received 4 May 2017).
NCT03174002 {published data only}
NCT03174002. Handling oxygenation targets in the intensive care unit (HOT‐ICU). clinicaltrials.gov/ct2/show/NCT03174002 (first received 2 June 2017).
NCT03287466 {published data only}
Targeted OXYgen therapy in critical illness (TOXYC). clinicaltrials.gov/ct2/show/NCT03287466 (first received 19 September 2017).
Additional references:
AARC 2002
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. [PUBMED: 12078655]
ACTRN12613000505707
ACTRN12613000505707. Feasibility and safety of conservative versus liberal oxygen targets in the mechanically ventilated patients. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364185 (first received 5 May 2013).
ACTRN12615000957594
ACTRN12615000957594. 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?id=369229&isReview=true (first received 1 September 2015).
Adhikari 2010
Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet 2010;376(9749):1339‐46. [PUBMED: 20934212]
Alba 2016
Alba AC, Alexander PE, Chang J, MacIsaac J, DeFry S, Guyatt GH. High statistical heterogeneity is more frequent in meta‐analysis of continuous than binary outcomes. Journal of Clinical Epidemiology 2016;70:129‐35. [PUBMED: 26386323]
ARC 2014
Australian Resuscitation Council. Guideline 11.6.1. Targeted oxygen therapy in adult advanced life support, 2014. resus.org.au/download/section_11/anzcor‐guideline‐11‐6‐1‐targeted‐oxygen‐therapy‐jan16.pdf (accessed 17 December 2015).
ARDS Definition Task Force 2012
ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012;307(23):2526‐33. [PUBMED: 22797452]
ARDS Network 2000
Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New England Journal of Medicine 2000;342(18):1301‐8. [PUBMED: 10793162]
ATS 2005
American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital‐acquired, ventilator‐associated, and healthcare‐associated pneumonia. American Journal of Respiratory and Critical Care Medicine 2005;171(4):388‐416. [PUBMED: 15699079]
Bailey 2003
Bailey TC, Martin EL, Zhao L, Veldhuizen RA. High oxygen concentrations predispose mouse lungs to the deleterious effects of high stretch ventilation. Journal of Applied Physiology 2003;94(3):975‐82. [PUBMED: 12571129]
Barbateskovic 2018
Barbateskovic M, Schjørring OL, Jakobsen JC, Meyhoff CS, Rasmussen BS, Perner A, et al. Oxygen supplementation for critically ill patients ‐ a protocol for a systematic review. Acta Anaesthesiologica Scandinavica 2018;62(7):1020‐30. [PUBMED: 29708586]
Bayes factor calculator 2014
Jakobsen JC, Wetterslev J, Winkel P, Lange T, Gluud C. Bayes factor calculator. www.ctu.dk/tools‐and‐links/bayes‐factor‐calculation.aspx (accessed 13 August 2019).
Begg 1994
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50(4):1088‐101. [PUBMED: 7786990]
Bellomo 2011
Bellomo R, Bailey M, Eastwood GM, Nichol A, Pilcher D, Hart GK. Arterial hyperoxia and in‐hospital mortality after resuscitation from cardiac arrest. Critical Care 2011;15(2):R90. [PUBMED: 21385416]
Benoit 2002
Benoît Z, Wicky S, Fischer JF, Frascarolo P, Chapuis C, Spahn DR, et al. The effect of increased FIO(2) before tracheal extubation on postoperative atelectasis. Anesthesia and Analgesia 2002;95(6):1777‐81. [PUBMED: 12456458]
Brenner 2012
Brenner M, Stein D, Hu P, Kufera J, Wooford M, Scalea T. Association between early hyperoxia and worse outcomes after traumatic brain injury. Archives of Surgery 2012;147(11):1042‐6. [PUBMED: 22801994]
Brok 2008
Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta‐analyses. Journal of Clinical Epidemiology 2008;61(8):763‐9. [PUBMED: 18411040]
Brok 2009
Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta‐analyses may be inconclusive ‐ trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta‐analyses. International Journal of Epidemiology 2009;38(1):287‐98. [PUBMED: 18824466]
Brower 2004
Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, et al. Higher versus lower positive end‐expiratory pressures in patients with the acute respiratory distress syndrome. New England Journal of Medicine 2004;351(4):327‐36. [PUBMED: 15269312]
Budinger 2013
Budinger GR, Mutlu GM. Balancing the risks and benefit of oxygen therapy in critically ill adults. Chest 2013;143(4):1151‐62. [PUBMED: 23546490]
Cabello 2016
Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database of Systematic Reviews 2016, Issue 12. [DOI: 10.1002/14651858.CD007160.pub4]
Chow 2003
Chow CW, Herrera Abreu MT, Suzuki T, Downey GP. Oxidative stress and acute lung injury. American Journal of Respiratory Cell and Molecular Biology 2003;29(4):427‐31. [PUBMED: 14500253]
Chu 2018
Chu DK, Kim LH, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta‐analysis. Lancet 2018;391(10131):1693‐705. [PUBMED: 29726345]
Crapo 1986
Crapo JD. Morphologic changes in pulmonary oxygen toxicity. Annual Review of Physiology 1986;48:721‐31. [PUBMED: 3518622]
Crapo 1999
Crapo RO, Jensen RL, Hegewald M, Tashkin DP. Arterial blood gas reference values for sea level and an altitude of 1,400 meters. American Journal of Respiratory and Critical Care Medicine 1999;160:1525‐31. [PUBMED: 10556115]
Dahl 2015
Dahl RM, Grønlykke L, Haase N, Holst LB, Perner A, Wetterslev J, et al. Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock. Acta Anaesthesiologica Scandinavia 2015;59(7):859‐69. [PUBMED: 25914095]
Damiani 2014
Damiani E, Adrario E, Girardis M, Romano R, Pelaia P, Singer M, et al. Arterial hyperoxia and mortality in critically ill patients: a systematic review and meta‐analysis. Critical Care 2014;18(6):711. [PUBMED: 25532567]
de Graaff 2011
de Graaff AE, Dongelmans DA, Binnekade JM, de Jonge E. Clinicians' response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2. Intensive Care Medicine 2011;37(1):46‐51. [PUBMED: 20878146]
de Jonge 2008
de Jonge E, Peelen L, Keijzers PJ, Joore H, de Lange D, van der Voort PH, et al. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Critical Care 2008;12(6):R156. [PUBMED: 19077208]
Deeks 2010
Deeks JJ, Higgins JPT. Statistical algorithms in Review Manager 5. https://training.cochrane.org/handbook/statistical‐methods‐revman52010:1‐11.
Dellinger 2013
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Critical Care Medicine 2013;41(2):580‐637. [PUBMED: 23353941]
DeMets 1987
DeMets DL. Methods for combining randomized clinical trials: strengths and limitations. Statistics in Medicine 1987;6(3):341‐50. [PUBMED: 3616287]
DerSimonian 1986
DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88. [PUBMED: 3802833]
Donahoe 2011
Donahoe M. Acute respiratory distress syndrome: a clinical review. Pulmonary Circulation 2011;1(2):192‐211. [PUBMED: 22034606]
Eastwood 2012
Eastwood G, Bellomo R, Bailey M, Taori G, Pilcher D, Young P, et al. Arterial oxygen tension and mortality in mechanically ventilated patients. Intensive Care Medicine 2012;38(1):91‐8. [PUBMED: 22127482]
Egger 1997
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315(7109):629‐34. [PUBMED: 9310563]
Esan 2010
Esan A, Hess DR, Raoof S, George L, Sessler CN. Severe hypoxemic respiratory failure: part 1 ‐ ventilatory strategies. Chest 2010;137(5):1203‐16. [PUBMED: 20442122]
Garattini 2016
Garattini S, Jakobsen JC, Wetterslev J, Bertelé V, Banzi R, Rath A, et al. Evidence‐based clinical practice: overview of threats to the validity of evidence and how to minimise them. European Journal of Internal Medicine 2016;32:13‐21. [PUBMED: 27160381]
Gilbert‐Kawai 2014
Gilbert‐Kawai ET, Mitchell K, Martin D, Carlisle J, Grocott MPW. Permissive hypoxaemia versus normoxaemia for mechanically ventilated critically ill patients. Cochrane Database of Systematic Reviews 2014, Issue 5. [DOI: 10.1002/14651858.CD009931.pub2]
Gluud 2011
Gluud C, Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G. User manual for Trial Sequential Analysis (TSA). www.ctu.dk/tsa/files/tsa_manual.pdf(accessed February 2016).
GRADEpro GDT [Computer program]
McMaster University (developed by Evidence Prime). GRADEpro GDT. Version accessed 25 March 2019. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015.
Guyatt 2008
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924‐6. [PUBMED: 18436948]
Hafner 2015
Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care, emergency, and peri‐operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Annals of Intensive Care 2015;5(1):42. [PUBMED: 26585328]
Harbord 2006
Harbord RM, Egger M, Sterne JA. A modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints. Statistics in Medicine 2006;25(20):3443‐57. [PUBMED: 16345038]
Helmerhorst 2015
Helmerhorst HJ, Roos‐Blom MJ, van Westerloo DJ, de Jonge E. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta‐analysis, and meta‐regression of cohort studies. Critical Care Medicine 2015;43(7):1508‐19. [PUBMED: 25855899]
Helmerhorst 2017a
Helmerhorst HJ, Arts DL, Schultz MJ, van der Voort PH, Abu‐Hanna A, de Jonge E, et al. Metrics of arterial hyperoxia and associated outcomes in critical care. Critical Care Medicine 2017;45(2):187‐95. [PUBMED: 27763912]
Helmerhorst 2017b
Helmerhorst HJF, Schouten LRA, Wagenaar GTM, Juffermans NP, Roelofs JJTH, Schultz MJ, et al. Hyperoxia provokes a time‐ and dose‐dependent inflammatory response in mechanically ventilated mice, irrespective of tidal volumes. Intensive Care Medicine Experimental 2017;5(1):27. [PUBMED: 28550659]
Higgins 2002
Higgins JP, Spiegelhalter DJ. Being sceptical about meta‐analyses: a Bayesian perspective on magnesium trials in myocardial infarction. International Journal of Epidemiology 2002;31(1):96‐104. [PUBMED: 11914302]
Higgins 2003
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. [PUBMED: 12958120]
Higgins 2011a
Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2011b
Higgins JP, Whitehead A, Simmonds M. Sequential methods for random‐effects meta‐analysis. Statistics in Medicine 2011;30(9):903‐21. [PUBMED: 21472757]
Hrobjartsson 2014
Hrobjartsson A, Emanuelsson F, Skou Thomsen AS, Hilden J, Brorson S. Bias due to lack of patient blinding in clinical trials. A systematic review of trials randomizing patients to blind and nonblind sub‐studies. International Journal of Epidemiology 2014;43(4):1272‐83. [PUBMED: 24881045]
ICH‐GCP 1997
International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH) adopts consolidated guideline on good clinical practice in the conduct of clinical trials on medicinal products for human use. International Digest of Health Legislation 1997;48(2):231‐4. [PUBMED: 11656783]
Imberger 2015
Imberger G, Gluud C, Boylan J, Wetterslev J. Systematic reviews of anesthesiologic interventions reported as statistically significant: problems with power, precision, and type 1 error protection. Anesthesia and Analgesia 2015;121(6):1611‐22. [PUBMED: 26579662]
Imberger 2016
Imberger G, Thorlund K, Gluud C, Wetterslev J. False‐positive findings in Cochrane meta‐analyses with and without application of trial sequential analysis: an empirical review. BMJ Open 2016;6(8):e011890. [PUBMED: 27519923]
IRCT201212199647N2
IRCT201212199647N2. Effect of high percent oxygen therapy in compared without oxygen therapy on rehabilitation in the first 12 hours of admission in patients with stroke: a randomized clinical trial. en.irct.ir/trial/10208 (first received 3 November 2013).
Itagaki 2015
Itagaki T, Nakano Y, Okuda N, Izawa M, Onodera M, Imanaka H, et al. Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and related factors. Respiratory Care 2015;60(3):335‐40. [PUBMED: 25389354]
Jakobsen 2013
Jakobsen JC, Gluud C. The necessity of randomized clinical trials. British Journal of Medicine and Medical Research 2013;3(4):1453‐68. [DOI: 10.9734/BJMMR/2013/3208]
Jakobsen 2014a
Jakobsen JC, Wetterslev J, Winkel P, Lange T, Gluud C. Thresholds for statistical and clinical significance in systematic reviews with meta‐analytic methods. BMC Medical Research Methodology 2014;14:120. [PUBMED: 25416419]
Jakobsen 2014b
Jakobsen JC, Gluud C, Winkel P, Lange T, Wetterslev J. The thresholds for statistical and clinical significance – a five‐step procedure for evaluation of intervention effects in randomised clinical trials. BMC Medical Research Methodology 2014;14:34. [DOI: 10.1186/1471‐2288‐14‐34]
Jakobsen 2016
Jakobsen JC, Wetterslev J, Lange T, Gluud C. Viewpoint: taking into account risks of random errors when analysing multiple outcomes in systematic reviews [editorial]. www.cochranelibrary.com/cdsr/doi/10.1002/14651858.ED000111/full 18 March 2016. [DOI: 10.1002/14651858.ED000111; PUBMED: 27030037]
Kahn 2010
Kahn JM, Benson NM, Appleby D, Carson SS, Iwashyna TJ. Long‐term acute care hospital utilization after critical illness. JAMA 2010;303(22):2253‐9. [PUBMED: 20530778]
Kallet 2013
Kallet RH, Matthay MA. Hyperoxic acute lung injury. Respiratory Care 2013;58(1):123‐41. [PUBMED: 23271823]
Kenmure 1971
Kenmure AC, Beatson JM, Cameron AJ, Horton PW. Effects of oxygen on myocardial blood flow and metabolism. Cardiovascular Research 1971;5(4):483‐9. [PUBMED: 5160452]
Kent 2011
Kent BD, Mitchell PD, McNicholas WT. Hypoxemia in patients with COPD: cause, effects, and disease progression. International Journal of COPD 2011;6:199‐208. [PUBMED: 21660297]
Kilgannon 2010
Kilgannon JH, Jones AE, Shapiro NI, Angelos MG, Milcarek B, Hunter K, et al. Association between arterial hyperoxia following resuscitation from cardiac arrest and in‐hospital mortality. JAMA 2010;303(21):2165‐71. [PUBMED: 20516417]
Kraft 2018
Kraft F, Andel H, Gamper J, Markstaller K, Ullrich R, Klein KU. Incidence of hyperoxia and related in‐hospital mortality in critically ill patients: a retrospective data analysis. Acta Anaesthesiologica Scandinavica 2018;62(3):347‐56. [PUBMED: 29210062]
Kratz 2004
Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. New England Journal of Medicine 2004;351(15):1548‐63. [PUBMED: 15470219]
Kulinskaya 2014
Kulinskaya E, Wood E. Trial sequential methods for meta‐analysis. Research Synthesis Methods 2014;5(3):212‐20. [PUBMED: 26052847]
MAGIC 2002
Magnesium in Coronaries (MAGIC) Trial Investigators. Early administration of intravenous magnesium to high‐risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Lancet 2002;360(9341):1189‐96. [PUBMED: 12401244]
Mantel 1959
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute 1959;22(4):719‐48. [PUBMED: 13655060]
Mascha 2015
Mascha EJ. Alpha, beta, meta: guidelines for assessing power and type I error in meta‐analyses. Anesthesia and Analgesia 2015;121(6):1430‐3. [DOI: 10.1213/ANE.0000000000000993; PUBMED: 26579648]
Metnitz 2009
Metnitz PG, Metnitz B, Moreno RP, Bauer P, Del Sorbo L, Hoermann C, et al. Epidemiology of mechanical ventilation: analysis of the SAPS 3 database. Intensive Care Medicine 2009;35(5):816‐25. [PUBMED: 19288079]
Meyhoff 2012
Meyhoff CS, Jorgensen LN, Wetterslev J, Christensen KB, Rasmussen LS, PROXI Trial Group. Increased long‐term mortality after a high perioperative inspiratory oxygen fraction during abdominal surgery: follow‐up of a randomized clinical trial. Anesthesia and Analgesia 2012;115(4):849‐54. [PUBMED: 22798533]
NCT01201291
NCT01201291. Impact of Inspired Oxygen Fraction on Outcome in Patients With Traumatic Brain Injury (BRAINOXY). clinicaltrials.gov/ct2/show/NCT01201291 (first received 14 September 2010).
NCT01319643
NCT01319643. Normal Oxygenation Versus Hyperoxia in the Intensive Care Unit (ICU) (OXYGEN‐ICU). clinicaltrials.gov/ct2/show/NCT01319643 (first received 22 March 2011).
NCT01722422
NCT01722422. Hyperoxia and Hypertonic Saline in Septic Shock (Hyper2S). clinicaltrials.gov/ct2/show/study/NCT01722422 (first received 6 November 2012).
NCT02698917
NCT02698917. Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation (COMACARE). https://clinicaltrials.gov/ct2/show/NCT02698917 (first received 4 March 2016).
O'Driscoll 2017
O'Driscoll BR, Howard LS, Earis J, Mak V, British Thoracic Society Emergency Oxygen Guideline Group, BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax 2017;72(Suppl 1):ii1‐90. [PUBMED: 28507176]
Pannu 2016
Pannu SR, Dziadzko MA, Gajic O. How much oxygen? Oxygen titration goals during mechanical ventilation. American Journal of Respiratory and Critical Care Medicine 2016;193(1):4‐5. [DOI: 10.1164/rccm.201509‐1810ED; PUBMED: 26720783]
Panwar 2013
Panwar R, Capellier G, Schmutz N, Davies A, Cooper DJ, Bailey M, et al. Current oxygenation practice in ventilated patients ‐ an observational cohort study. Anaesthesia and Intensive Care 2013;41(4):505‐14. [PUBMED: 23808511]
Panwar 2015
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. [PUBMED: 26334785]
Petersson 2014
Petersson J, Glenny RW. Gas exchange and ventilation‐perfusion relationships in the lung. European Respiratory Journal 2014;44(4):1023‐41. [PUBMED: 25063240]
Pocock 2015
Pocock SJ, Clayton TC, Stone GW. Design of major randomized trials: part 3 of a 4‐part series on statistics for clinical trials. Journal of the American College of Cardiology 2015;66(24):2757‐66. [PUBMED: 26700838]
Pogue 1997
Pogue JM, Yusuf S. Cumulating evidence from randomized trials: utilizing sequential monitoring boundaries for cumulative meta‐analysis. Controlled Clinical Trials 1997;18(6):580‐93. [PUBMED: 9408720]
Rachmale 2012
Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respiratory Care 2012;57(11):1887‐93. [PUBMED: 22613692]
Raj 2013
Raj R, Bendel S, Reinikainen M, Kivisaari R, Siironen J, Lång M, et al. Hyperoxemia and long‐term outcome after traumatic brain injury. Critical Care 2013;17(4):R177. [PUBMED: 23958227]
Raoof 2010
Raoof S, Goulet K, Esan A, Hess DR, Sessler CN. Severe hypoxemic respiratory failure: part 2 ‐ nonventilatory strategies. Chest 2010;137(6):1437‐48. [PUBMED: 20525656]
Rasmussen 2018
Rasmussen BS, Perner A, Wetterslev J, Meyhoff CS, Schjørring OL. Oxygenation targets in acutely ill patients: still a matter of debate. Lancet 2018;392(10163):2436‐7. [PUBMED: 30527413]
Review Manager 2014 [Computer program]
Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rodríguez‐Roisin 2005
Rodríguez‐Roisin R, Roca J. Mechanisms of hypoxemia. Intensive Care Medicine 2005;31(8):1017‐9. [PUBMED: 16052273]
Rothen 1995a
Rothen HU, Sporre B, Engberg G, Wegenius G, Högman M, Hedenstierna G. Influence of gas composition on recurrence of atelectasis after a reexpansion maneuver during general anesthesia. Anesthesiology 1995;82(4):832‐42. [PUBMED: 7717553]
Rothen 1995b
Rothen HU, Sporre B, Engberg G, Wegenius G, Reber A, Hedenstierna G. Prevention of atelectasis during general anaesthesia. Lancet 1995;345(8962):1387‐91. [PUBMED: 7760608]
Roussos 2003
Roussos C, Koutsoukou A. Respiratory failure. European Respiratory Journal 2003;47:3S‐14S. [PUBMED: 14621112]
Sacco 2013
Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44(7):2064‐89. [PUBMED: 23652265]
Savovic 2018
Savovic J, Turner RM, Mawdsley D, Jones HE, Beynon R, Higgins JPT, et al. Association between risk‐of‐bias assessments and results of randomized trials in Cochrane Reviews: the ROBES meta‐epidemiologic study. American Journal of Epidemiology 2018;187(5):1113‐22. [PUBMED: 29126260]
Schjørring 2018
Schjørring OL, Toft‐Petersen AP, Kusk KH, Mouncey P, Sørensen EE, Berezowicz P, et al. Intensive care doctors' preferences for arterial oxygen tension levels in mechanically ventilated patients. Acta Anaesthesiologica Scandinavica 2018;62(10):1443‐51. [PUBMED: 29926908]
Sepehrvand 2018
Sepehrvand N, James SK, Stub D, Khoshnood A, Ezekowitz JA, Hofmann R. Effects of supplemental oxygen therapy in patients with suspected acute myocardial infarction: a meta‐analysis of randomised clinical trials. Heart 2018;104(20):1694‐8. [PUBMED: 29599378]
Siemieniuk 2018
Siemieniuk RAC, Chu DK, Kim LH, Güell‐Rous MR, Alhazzani W, Soccal PM, et al. Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ 2018;363:k4169. [PUBMED: 30355567]
Sinclair 2004
Sinclair SE, Altemeier WA, Matute‐Bello G, Chi EY. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Critical Care Medicine 2004;32(12):2496‐501. [PUBMED: 15599157]
Sjöberg 2013
Sjöberg F, Singer M. The medical use of oxygen: a time for critical reappraisal. Journal of Internal Medicine 2013;274(6):505‐28. [DOI: 10.1111/joim.12139; PUBMED: 24206183]
Suzuki 2013
Suzuki S, Eastwood GM, Peck L, Glassford NJ, Bellomo R. Current oxygen management in mechanically ventilated patients: a prospective observational cohort study. Journal of Critical Care 2013;28(5):647‐54. [PUBMED: 23683560]
Tan 2014
Tan HL, Wijeweera O. Oxygen in critical care. Trends in Anaesthesia and Critical Care 2014;4:102‐8. [DOI: 10.1016/j.tacc.2014.05.001]
Terkawi 2016
Terkawi AS, Mavridis D, Flood P, Wetterslev J, Terkawi RS, Bin Abdulhak AA, et al. Does ondansetron modify sympathectomy due to subarachnoid anesthesia?: meta‐analysis, meta‐regression, and trial sequential analysis. Anesthesiology 2016;124(4):846‐69. [DOI: 10.1097/ALN.0000000000001039; PUBMED: 26835645]
Thorlund 2009
Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JPA, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta‐analyses?. International Journal of Epidemiology 2009;38(1):276‐86. [PUBMED: 18824467]
Thygesen 2012
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Circulation 2012;126(16):2020‐35. [PUBMED: 22923432]
TSA 2011 [Computer program]
Copenhagen Trial Unit. TSA ‐ Trial Sequential Analysis. Version 0.9 Beta. Copenhagen: Copenhagen Trial Unit, 2011.
Turner 2013
Turner RM, Bird SM, Higgins JP. The impact of study size on meta‐analyses: examination of underpowered studies in Cochrane reviews. PLOS ONE 2013;8(3):e59202. [PUBMED: 23544056]
Wagner 1977
Wagner PD, Dantzker DR, Dueck R, Clausen JL, West JB. Ventilation‐perfusion inequality in chronic obstructive pulmonary disease. Journal of Clinical Investigation 1977;59(2):203‐16. [PUBMED: 833271]
Watson 2000
Watson NA, Beards SC, Altaf N, Kassner A, Jackson A. The effect of hyperoxia on cerebral blood flow: a study in healthy volunteers using magnetic resonance phase‐contrast angiography. European Journal of Anaesthesiology 2000;17(3):152‐9. [PUBMED: 10758463]
Wetterslev 2008
Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta‐analysis. Journal of Clinical Epidemiology 2008;61(1):64‐75. [PUBMED: 18083463]
Wetterslev 2009
Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in random‐effects model meta‐analyses. BMC Medical Research Methodology 2009;9:86. [PUBMED: 20042080]
Wetterslev 2015
Wetterslev J, Meyhoff CS, Jørgensen LN, Gluud C, Lindschou J, Rasmussen LS. The effects of high perioperative inspiratory oxygen fraction for adult surgical patients. Cochrane Database of Systematic Reviews 2015, Issue 6. [DOI: 10.1002/14651858.CD008884.pub2]
Whitehead 2002
Whitehead T, Slutsky AS. The pulmonary physician in critical care ᛫ 7: ventilator induced lung injury. Thorax 2002;57(7):635‐42. [PUBMED: 12096209]
Woods 2002
Woods KL, Abrams K. The importance of effect mechanism in the design and interpretation of clinical trials: the role of magnesium in acute myocardial infarction. Progress in Cardiovascular Diseases 2002;44(4):267‐74. [PUBMED: 12007082]
Wunsch 2010
Wunsch H, Linde‐Zwirble WT, Angus DC, Hartman ME, Milbrandt EB, Kahn JM. The epidemiology of mechanical ventilation use in the United States. Critical Care Medicine 2010;38(10):1947‐53. [PUBMED: 20639743]
You 2018
You J, Fan X, Bi X, Xian Y, Xie D, Fan M, et al. Association between arterial hyperoxia and mortality in critically ill patients: a systematic review and meta‐analysis. Journal of Critical Care 2018;47:260‐8. [PUBMED: 30077082]
Young 2012
Young P, Beasley R, Bailey M, Bellomo R, Eastwood GM, Nichol A, et al. The association between early arterial oxygenation and mortality in ventilated patients with acute ischaemic stroke. Critical Care and Resuscitation 2012;14(1):14‐9. [PUBMED: 22404056]
Zaher 2007
Zaher TE, Miller EJ, Morrow DM, Javdan M, Mantell LL. Hyperoxia‐induced signal transduction pathways in pulmonary epithelial cells. Free Radical Biology and Medicine 2007;42(7):897‐908. [PUBMED: 17349918]
Zhang 2016
Zhang Z, Ji X. Quadratic function between arterial partial oxygen pressure and mortality risk in sepsis patients: an interaction with simplified acute physiology score. Scientific Reports 2016;6:35133. [PUBMED: 27734905]
References to other published versions of this review:
Barbateskovic 2017
Barbateskovic M, Schjørring OL, Jakobsen JC, Meyhoff CS, Dahl RM, Rasmussen BS, et al. Higher versus lower inspiratory oxygen fraction or targets of arterial oxygenation for adult intensive care patients. Cochrane Database of Systematic Reviews 2017, Issue 4. [DOI: 10.1002/14651858.CD012631]
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2021 JBMEDE - Jornal Brasileiro de Medicina de Emergência
This work is licensed under a Creative Commons Attribution 4.0 International License.
