Early end for trial of experimental oxygenation strategies in ARDS

Background: Both observational studies and clinical trials have found that a liberal oxygenation strategy in multiple inpatient settings may be harmful. Furthermore, a conservative strategy is what has been recommended in guidelines. Conversely, the relevance of this recent concept has been challenged in a large trial of a critically ill population (ICU-ROX).

Study design: Randomized clinical trial, unblinded.

Setting: Thirteen sites in France.

Synopsis: In a multicenter randomized clinical trial, investigators enrolled patients with ARDS to either a liberal oxygenation group (PaO₂ target 90-105 mm Hg or SpO₂ of 96% or greater) or a conservative oxygenation group (PaO₂ target 55-70 mm Hg or SpO2 88%-92%). The trial was planned for inclusion of 850 patients, but the data and safety monitoring board decided to stop the trial after inclusion of 205 patients. Although the primary outcome (28-day all-cause mortality) was not significantly different between groups (34.3% vs 26.5%; absolute difference, 7.8%; 95% confidence interval, –4.8 to 20.6), the direction was signaling possible harm and there were five episodes of mesenteric ischemia in the conservative oxygenation group (none in the liberal oxygenation group).

Bottom line: A conservative oxygenation strategy cannot be currently recommended to patients with ARDS in the ICU. A minimum SpO₂ of 90% was suggested in an accompanying editorial.

Editorial commentary: Interestingly, the supplemental results of the article show that prone positioning was used much less frequently in the conservative oxygenation group (34.3 vs 51.0%). If the impressive results of Guerin (2013) would be repeated in this population, this difference could help explain the higher observed mortality in the conservative oxygenation group. It is possible that, by aiming to be less aggressive in improving the PaO₂, clinicians inadvertently withheld effective treatments for ARDS. The results of this trial bring up several interesting questions, but provide the bedside clinician with few answers. The complex interplay of treatment factors needs to be dissected in future trials.

Citation: Barrot L et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Eng J Med. 2020;382:999-1008.

Dr. Saraiva is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Both observational studies and clinical trials have found that a liberal oxygenation strategy in multiple inpatient settings may be harmful. Furthermore, a conservative strategy is what has been recommended in guidelines. Conversely, the relevance of this recent concept has been challenged in a large trial of a critically ill population (ICU-ROX).

Study design: Randomized clinical trial, unblinded.

Setting: Thirteen sites in France.

Synopsis: In a multicenter randomized clinical trial, investigators enrolled patients with ARDS to either a liberal oxygenation group (PaO₂ target 90-105 mm Hg or SpO₂ of 96% or greater) or a conservative oxygenation group (PaO₂ target 55-70 mm Hg or SpO2 88%-92%). The trial was planned for inclusion of 850 patients, but the data and safety monitoring board decided to stop the trial after inclusion of 205 patients. Although the primary outcome (28-day all-cause mortality) was not significantly different between groups (34.3% vs 26.5%; absolute difference, 7.8%; 95% confidence interval, –4.8 to 20.6), the direction was signaling possible harm and there were five episodes of mesenteric ischemia in the conservative oxygenation group (none in the liberal oxygenation group).

Bottom line: A conservative oxygenation strategy cannot be currently recommended to patients with ARDS in the ICU. A minimum SpO₂ of 90% was suggested in an accompanying editorial.

Editorial commentary: Interestingly, the supplemental results of the article show that prone positioning was used much less frequently in the conservative oxygenation group (34.3 vs 51.0%). If the impressive results of Guerin (2013) would be repeated in this population, this difference could help explain the higher observed mortality in the conservative oxygenation group. It is possible that, by aiming to be less aggressive in improving the PaO₂, clinicians inadvertently withheld effective treatments for ARDS. The results of this trial bring up several interesting questions, but provide the bedside clinician with few answers. The complex interplay of treatment factors needs to be dissected in future trials.

Citation: Barrot L et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Eng J Med. 2020;382:999-1008.

Dr. Saraiva is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Both observational studies and clinical trials have found that a liberal oxygenation strategy in multiple inpatient settings may be harmful. Furthermore, a conservative strategy is what has been recommended in guidelines. Conversely, the relevance of this recent concept has been challenged in a large trial of a critically ill population (ICU-ROX).

Study design: Randomized clinical trial, unblinded.

Setting: Thirteen sites in France.

Synopsis: In a multicenter randomized clinical trial, investigators enrolled patients with ARDS to either a liberal oxygenation group (PaO₂ target 90-105 mm Hg or SpO₂ of 96% or greater) or a conservative oxygenation group (PaO₂ target 55-70 mm Hg or SpO2 88%-92%). The trial was planned for inclusion of 850 patients, but the data and safety monitoring board decided to stop the trial after inclusion of 205 patients. Although the primary outcome (28-day all-cause mortality) was not significantly different between groups (34.3% vs 26.5%; absolute difference, 7.8%; 95% confidence interval, –4.8 to 20.6), the direction was signaling possible harm and there were five episodes of mesenteric ischemia in the conservative oxygenation group (none in the liberal oxygenation group).

Bottom line: A conservative oxygenation strategy cannot be currently recommended to patients with ARDS in the ICU. A minimum SpO₂ of 90% was suggested in an accompanying editorial.

Editorial commentary: Interestingly, the supplemental results of the article show that prone positioning was used much less frequently in the conservative oxygenation group (34.3 vs 51.0%). If the impressive results of Guerin (2013) would be repeated in this population, this difference could help explain the higher observed mortality in the conservative oxygenation group. It is possible that, by aiming to be less aggressive in improving the PaO₂, clinicians inadvertently withheld effective treatments for ARDS. The results of this trial bring up several interesting questions, but provide the bedside clinician with few answers. The complex interplay of treatment factors needs to be dissected in future trials.

Citation: Barrot L et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Eng J Med. 2020;382:999-1008.

Dr. Saraiva is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.