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Supplemental Oxygen Therapy in Medical Emergencies: More Harm Than Benefit?

Supplemental Oxygen Therapy in Medical Emergencies: More Harm Than Benefit? In medical emergencies, such as acute coronary syndrome, cardiopulmonary resuscitation (CPR), stroke, and exacerbations of chronic obstructive pulmonary disease (COPD), supplemental oxygen is often routinely administered. Most physicians believe this intervention is potentially lifesaving, and many guidelines support the routine use of high-dose supplemental oxygen. Over the decades, however, potential detrimental effects of supplemental oxygen appear to have been ignored. Many clinicians are unaware of the variety of preclinical studies that have been executed, showing that hyperoxia causes both coronary and systemic vasoconstriction, resulting in deterioration of several important (hemodynamic) parameters (Table). The prime candidate mechanism for these unintended effects is believed to be the formation of reactive oxygen species. In this Research Letter, we draw attention to the collective clinical evidence, which argues against the routine use of high-dose oxygen. Awaiting more thorough studies, we strongly recommend a policy of careful, titrated oxygen supplementation. Methods We conducted a search of the literature in MEDLINE and EMBASE to identify articles addressing the effect of oxygen therapy in acute coronary syndrome, cardiopulmonary resuscitation, stroke, and exacerbations of chronic obstructive pulmonary disease. Results Large (randomized) clinical studies addressing oxygen supplementation are scarce. In 1976, a double-blind randomized trial was performed in 200 patients with suspected acute myocardial infarction. In the supplemental oxygen group, 9 of 80 patients (11%) died, as opposed to 3 of 77 (3.9%) in patients breathing compressed air (relative risk [RR] of mortality, 2.9; 95% CI, 0.8-10.3). A recent Cochrane review combined this trial with a smaller similar one, which generated a composite RR of mortality of 3.03 (95% CI, 0.93-9.83).1 In acute decompensated heart failure, no clinical studies are available, despite the rather abundant evidence from preclinical studies, suggesting that such patients may experience the adverse effects caused by coronary and systemic vasoconstriction (Table). In accordance with existing guidelines, supplemental oxygen is often administered during CPR. In the postresuscitation phase, evidence exists that 30% oxygen is more brain protective than pure oxygen.2 Recently, an observational study in 6326 patients showed that supplemental oxygen induced postresuscitation hyperoxia was independently associated with increased mortality (odds ratio [OR], 1.8; 95% CI, 1.5-2.2). A subsequent analysis of the same cohort indicated that each 25–mm Hg increase in PaO2 was associated with a statistically significant 6% increase in the relative risk of death.3 Finally, a comparable cohort of 12 108 patients was analyzed in New Zealand and Australia. Again, the hyperoxia group showed an increased risk of mortality compared with the normoxia group (OR, 1.2; 95% CI, 1.1-1.6). Although the statistical significance of this finding was not maintained after multivariable adjustment, certainly no beneficial effects of hyperoxia were found.4 In the management of ischemic stroke, a randomized trial suggested that hyperbaric oxygen may adversely affect stroke severity.5 With regard to normobaric oxygen, 3 randomized trials were performed. One showed no benefit on clinical outcome.6 Another trial in nonhypoxic patients found lower survival at 1 year (OR, 0.45; 95% CI, 0.23-0.90) in those who received supplemental oxygen during initial treatment.7 The third randomized trial was terminated in 2009 after enrolling 85 patients because of excess mortality in the hyperoxia group (40% vs 17% [P = .01 by our own calculation]) (Clinical Trial of Normobaric Oxygen Therapy in Acute Ischemic Stroke [not published]; clinicaltrials.gov Identifier: NCT00414726). Although an external monitor judged the excess mortality as “unrelated to oxygen treatment,” these results are important because this was the largest randomized trial investigating oxygen treatment for ischemic stroke, and it is remarkable that these results have not (yet) been published. In the management of COPD, the risks of oxygen supplementation are widely acknowledged. Administration of oxygen in patients with COPD may cause hypercapnia due to ventilation-perfusion mismatching, the Haldane effect, inhibition of hypoxic drive, and atelectasis. Guidelines recommend a maximum FIO2 of 0.28. However, patients with COPD often receive higher doses, especially during ambulance transportation, causing hypercapnia and increased mortality. Recently, a randomized trial compared high concentration oxygen with titrated oxygen in prehospital patients with exacerbation of COPD. Mortality was lower in patients receiving titrated oxygen (RR, 0.42; 95% CI, 0.20-0.89). In those with later-confirmed COPD, mortality reduction was even stronger (RR, 0.22; 95% CI, 0.05-0.91).8 Comment In conclusion, there appear to be potential dangers of routine administration of supplemental oxygen during a variety of medical emergencies. Hyperoxia is associated with hemodynamic alterations that may increase myocardial ischemia and impair cardiac performance, and the results from relatively unknown preclinical studies appear to be supported by the available clinical evidence. Moreover, hyperoxia also seems to be associated with adverse outcomes in different noncardiac emergencies. Finally, in our extensive literature review, we did not find a single study contradicting the reported hazards of hyperoxia or, in fact, suggesting benefits. We acknowledge that additional clinical research is warranted to determine whether routine high-dose supplemental oxygen in medical emergencies indeed causes more harm than benefit. Until that time, however, we call for appropriate caution in applying supplemental oxygen. Hypoxemia should be treated carefully with stepwise increases in inhaled oxygen concentration in an attempt to avoid arterial hyperoxia. Back to top Article Information Correspondence: Dr Cornet, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands (cornet@vumc.nl). Published Online: January 9, 2012. doi:10.1001/archinternmed.2011.624 Author Contributions:Study concept and design: Cornet, Kooter, Peters, and Smulders. Acquisition of data: Cornet, Kooter, and Peters. Analysis and interpretation of data: Cornet, Kooter, and Peters. Drafting of the manuscript: Cornet, Kooter, Peters, and Smulders. Critical revision of the manuscript for important intellectual content: Cornet, Kooter, Peters, and Smulders. Administrative, technical, and material support: Cornet and Peters. Study supervision: Kooter and Smulders. Financial Disclosure: None reported. References 1. Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2010;(6):CD00716020556775PubMedGoogle Scholar 2. 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):199-20616500018PubMedGoogle ScholarCrossref 3. Kilgannon JH, Jones AE, Parillo JE, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Relationship between supranormal oxygen tension and outcome resuscitation from cardiac arrest. Circulation. 2011;123:2717-272221606393PubMedGoogle ScholarCrossref 4. Bellomo R, Bailey M, Eastwood GM, et al; Study of Oxygen in Critical Care (SOCC) Group. Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest. Crit Care. 2011;15(2):R9021385416PubMedGoogle ScholarCrossref 5. Rusyniak DE, Kirk MA, May JD, et al; Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study. Hyperbaric oxygen therapy in acute ischemic stroke: results of the Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study. Stroke. 2003;34(2):571-57412574578PubMedGoogle ScholarCrossref 6. Padma MV, Bhasin A, Bhatia R, et al. Normobaric oxygen therapy in acute ischemic stroke: a pilot study in Indian patients. Ann Indian Acad Neurol. 2010;13(4):284-28821264137PubMedGoogle ScholarCrossref 7. Rønning OM, Guldvog B. Should stroke victims routinely receive supplemental oxygen? a quasi-randomized controlled trial. Stroke. 1999;30(10):2033-203710512903PubMedGoogle ScholarCrossref 8. 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:c546220959284PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Supplemental Oxygen Therapy in Medical Emergencies: More Harm Than Benefit?

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References (8)

Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2011.624
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Abstract

In medical emergencies, such as acute coronary syndrome, cardiopulmonary resuscitation (CPR), stroke, and exacerbations of chronic obstructive pulmonary disease (COPD), supplemental oxygen is often routinely administered. Most physicians believe this intervention is potentially lifesaving, and many guidelines support the routine use of high-dose supplemental oxygen. Over the decades, however, potential detrimental effects of supplemental oxygen appear to have been ignored. Many clinicians are unaware of the variety of preclinical studies that have been executed, showing that hyperoxia causes both coronary and systemic vasoconstriction, resulting in deterioration of several important (hemodynamic) parameters (Table). The prime candidate mechanism for these unintended effects is believed to be the formation of reactive oxygen species. In this Research Letter, we draw attention to the collective clinical evidence, which argues against the routine use of high-dose oxygen. Awaiting more thorough studies, we strongly recommend a policy of careful, titrated oxygen supplementation. Methods We conducted a search of the literature in MEDLINE and EMBASE to identify articles addressing the effect of oxygen therapy in acute coronary syndrome, cardiopulmonary resuscitation, stroke, and exacerbations of chronic obstructive pulmonary disease. Results Large (randomized) clinical studies addressing oxygen supplementation are scarce. In 1976, a double-blind randomized trial was performed in 200 patients with suspected acute myocardial infarction. In the supplemental oxygen group, 9 of 80 patients (11%) died, as opposed to 3 of 77 (3.9%) in patients breathing compressed air (relative risk [RR] of mortality, 2.9; 95% CI, 0.8-10.3). A recent Cochrane review combined this trial with a smaller similar one, which generated a composite RR of mortality of 3.03 (95% CI, 0.93-9.83).1 In acute decompensated heart failure, no clinical studies are available, despite the rather abundant evidence from preclinical studies, suggesting that such patients may experience the adverse effects caused by coronary and systemic vasoconstriction (Table). In accordance with existing guidelines, supplemental oxygen is often administered during CPR. In the postresuscitation phase, evidence exists that 30% oxygen is more brain protective than pure oxygen.2 Recently, an observational study in 6326 patients showed that supplemental oxygen induced postresuscitation hyperoxia was independently associated with increased mortality (odds ratio [OR], 1.8; 95% CI, 1.5-2.2). A subsequent analysis of the same cohort indicated that each 25–mm Hg increase in PaO2 was associated with a statistically significant 6% increase in the relative risk of death.3 Finally, a comparable cohort of 12 108 patients was analyzed in New Zealand and Australia. Again, the hyperoxia group showed an increased risk of mortality compared with the normoxia group (OR, 1.2; 95% CI, 1.1-1.6). Although the statistical significance of this finding was not maintained after multivariable adjustment, certainly no beneficial effects of hyperoxia were found.4 In the management of ischemic stroke, a randomized trial suggested that hyperbaric oxygen may adversely affect stroke severity.5 With regard to normobaric oxygen, 3 randomized trials were performed. One showed no benefit on clinical outcome.6 Another trial in nonhypoxic patients found lower survival at 1 year (OR, 0.45; 95% CI, 0.23-0.90) in those who received supplemental oxygen during initial treatment.7 The third randomized trial was terminated in 2009 after enrolling 85 patients because of excess mortality in the hyperoxia group (40% vs 17% [P = .01 by our own calculation]) (Clinical Trial of Normobaric Oxygen Therapy in Acute Ischemic Stroke [not published]; clinicaltrials.gov Identifier: NCT00414726). Although an external monitor judged the excess mortality as “unrelated to oxygen treatment,” these results are important because this was the largest randomized trial investigating oxygen treatment for ischemic stroke, and it is remarkable that these results have not (yet) been published. In the management of COPD, the risks of oxygen supplementation are widely acknowledged. Administration of oxygen in patients with COPD may cause hypercapnia due to ventilation-perfusion mismatching, the Haldane effect, inhibition of hypoxic drive, and atelectasis. Guidelines recommend a maximum FIO2 of 0.28. However, patients with COPD often receive higher doses, especially during ambulance transportation, causing hypercapnia and increased mortality. Recently, a randomized trial compared high concentration oxygen with titrated oxygen in prehospital patients with exacerbation of COPD. Mortality was lower in patients receiving titrated oxygen (RR, 0.42; 95% CI, 0.20-0.89). In those with later-confirmed COPD, mortality reduction was even stronger (RR, 0.22; 95% CI, 0.05-0.91).8 Comment In conclusion, there appear to be potential dangers of routine administration of supplemental oxygen during a variety of medical emergencies. Hyperoxia is associated with hemodynamic alterations that may increase myocardial ischemia and impair cardiac performance, and the results from relatively unknown preclinical studies appear to be supported by the available clinical evidence. Moreover, hyperoxia also seems to be associated with adverse outcomes in different noncardiac emergencies. Finally, in our extensive literature review, we did not find a single study contradicting the reported hazards of hyperoxia or, in fact, suggesting benefits. We acknowledge that additional clinical research is warranted to determine whether routine high-dose supplemental oxygen in medical emergencies indeed causes more harm than benefit. Until that time, however, we call for appropriate caution in applying supplemental oxygen. Hypoxemia should be treated carefully with stepwise increases in inhaled oxygen concentration in an attempt to avoid arterial hyperoxia. Back to top Article Information Correspondence: Dr Cornet, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands (cornet@vumc.nl). Published Online: January 9, 2012. doi:10.1001/archinternmed.2011.624 Author Contributions:Study concept and design: Cornet, Kooter, Peters, and Smulders. Acquisition of data: Cornet, Kooter, and Peters. Analysis and interpretation of data: Cornet, Kooter, and Peters. Drafting of the manuscript: Cornet, Kooter, Peters, and Smulders. Critical revision of the manuscript for important intellectual content: Cornet, Kooter, Peters, and Smulders. Administrative, technical, and material support: Cornet and Peters. Study supervision: Kooter and Smulders. Financial Disclosure: None reported. References 1. Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2010;(6):CD00716020556775PubMedGoogle Scholar 2. 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):199-20616500018PubMedGoogle ScholarCrossref 3. Kilgannon JH, Jones AE, Parillo JE, et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Relationship between supranormal oxygen tension and outcome resuscitation from cardiac arrest. Circulation. 2011;123:2717-272221606393PubMedGoogle ScholarCrossref 4. Bellomo R, Bailey M, Eastwood GM, et al; Study of Oxygen in Critical Care (SOCC) Group. Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest. Crit Care. 2011;15(2):R9021385416PubMedGoogle ScholarCrossref 5. Rusyniak DE, Kirk MA, May JD, et al; Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study. Hyperbaric oxygen therapy in acute ischemic stroke: results of the Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study. Stroke. 2003;34(2):571-57412574578PubMedGoogle ScholarCrossref 6. Padma MV, Bhasin A, Bhatia R, et al. Normobaric oxygen therapy in acute ischemic stroke: a pilot study in Indian patients. Ann Indian Acad Neurol. 2010;13(4):284-28821264137PubMedGoogle ScholarCrossref 7. Rønning OM, Guldvog B. Should stroke victims routinely receive supplemental oxygen? a quasi-randomized controlled trial. Stroke. 1999;30(10):2033-203710512903PubMedGoogle ScholarCrossref 8. 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:c546220959284PubMedGoogle ScholarCrossref

Journal

Archives of Internal Medicine – American Medical Association

Published: Feb 13, 2012

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