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ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Chu DK, Kim LH, Young PJ, 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;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, 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;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, 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;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Chu DK, Kim LH, Young PJ, 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;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, 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;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, 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;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
1. Chu DK, Kim LH, Young PJ, 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;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, 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;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, 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;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
PRACTICE CHANGER
Do not use liberal oxygen therapy (SpO2 > 96%) in acutely ill adults, as it is associated with increased all-cause mortality.1
STRENGTH OF RECOMMENDATION
A: Based on a systematic review and meta-analysis of 25 randomized controlled trials.
Chu DK, Kim LH, Young PJ, 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;391:1693-1705.
