Higher vs. lower oxygen strategies: No difference in 90-day mortality while lower oxygenation reduces adverse events

Netherlands: A study published in the Journal of Critical Care has highlighted no difference in 90-day mortality between higher and lower oxygen strategies. However, a lower incidence of serious adverse events is associated with lower oxygen strategies.

The literature mentions the effectiveness of oxygen therapy for hypoxia, but it may not benefit all patients. The harmful effects of oxygen are acknowledgeable and occur when the patient is exposed to very high concentrations of oxygen for a short duration or to lower concentrations of oxygen for a more extended period. This may result in acute (CNS effects) and chronic (Pulmonary effects) oxygen toxicity, causing cell damage and death.

While the new guidelines recommend a conservative approach, the trials comparing higher versus lower oxygen targets show mixed and unrelated results.

Based on the above background, a study was conducted by a team of researchers led by Dr. Lee from the Department of Critical care of Leiden University Medical Centre in which the pieces of evidence were collected from those RCTs, which made a comparison between higher and lower oxygen strategies in ICU patients. The present study attempted to highlight favorable oxygen therapy more conclusively and definitively.

The studies mentioning the comparison between higher and lower oxygen strategies were searched in MEDLINE, EMBASE, and Web of Science. The primary outcome was 90-day mortality, while secondary outcomes included severe adverse events (SAE), support-free days, and length of stay (LOS).

The critical points of the study are:

• 68 full-text articles were screened to match the eligibility criteria.

• Nine studies with 5807 patients were included in the final analysis.

• The main focus of the search strategy was to include RCT comparing higher vs. lower approach focusing on the general ICU population.

• Parameters used to pursue oxygenation targets were PaO2, SpO2, FiO2, or a combination.

• The range of interventions was 24 h to 90 days.

• No significant difference was recorded for 90-day mortality in the oxygenation strategies with an Odds Ratio of 1.01.

• GRADE approach rated certainty of evidence as low.

• OR for day 28 was 0.94 (very low certainty), 1.05 for day 180 ( low certainty), 0.90 for ICU mortality (low certainty), and 0.86 for hospital mortality (very low certainty), suggesting no significant difference.

• The OR for respiratory infection was 0.88, 1.29 for myocardial ischemia, 1.12 for intestinal ischemia, and 0.94 for ischemic stroke.

• The OR was 0.86 for the incidence of adverse events favoring lower targets, and the certainty of the evidence was graded very low.

• Lower oxygenation was associated with a reduced incidence of serious adverse events with an OR of 0.86.

• The support-free days had a mean difference of 0.20, which was insignificant and graded very low.

• The hospital LOS had a mean difference of −0.19 (very low certainty), while for ICU LOS, it was −0.64 (very low certainty).

Dr. Grim, MD, added, "Our systematic review and meta-analysis analyzed no difference in 90-day mortality between the two strategies. In secondary outcomes, we recorded a significant finding favoring lower oxygenation targets related to reduced serious adverse events."

The researchers said our study has strength and should be considered the most recent and updated, using a unique novel meta-regression analysis and a meta-analysis.

They wrote," The PRISMA and GRADE approach ensures the quality of our methodology, and the GRADE approach is lacking in earlier published meta-analyses." They concluded, "We did not report the difference between the two oxygen strategies for 90-day mortality, support-free days, and ICU and hospital LOS. At the same time, serious adverse events had a lower incidence with lower oxygenation. The findings of our study highlight clinical implications for practice guidelines. More trials should be conducted comparing the groups with relevancy on important adverse outcomes."

Further reading:

Higher versus lower oxygenation strategies in the general intensive care unit population: A systematic review, meta-analysis, and meta-regression of randomized controlled trials. Panel. Journal of Critical Care Volume 72, December 2022, 154151