Conservative Versus Higher Oxygen Targets Post-Cardiac Arrest: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.

Abstract

Background: Optimal oxygenation following return of spontaneous circulation (ROSC) remains uncertain, as both hypoxemia and hyperoxemia risk secondary injury. We conducted an updated systematic review and meta-analysis comparing the efficacy of restrictive versus higher oxygenation targets.

Methods: A systematic review and meta-analysis following the PRISMA 2020 protocol was carried out from database inception through June 2026. Only RCTs examining the impact of restrictive oxygenation versus higher oxygenation for adult CA patients undergoing invasive mechanical ventilation were included. Risks of bias and the quality of the evidence were evaluated using RoB 2 and GRADE tools. A random-effects model was used for data synthesis and presented the results in RR/MD.

Results: Eleven RCTs (12 reports) involving 4136 participants were included. Restrictive oxygenation showed no significant difference in all-cause mortality (RR 0.96, 95% CI 0.88-1.06) or unfavorable neurological outcomes (RR 0.96, 95% CI 0.88-1.04). Most subgroup analyses were non-significant, except for reduced mortality in the strict hypothermia subgroup (33°C-34°C), although TSA showed unstable evidence. No significant differences were observed in secondary outcomes. Restrictive oxygenation increased hypoxemia risk (RR 1.65) but improved ventilator-free days (MD 2.14).

Conclusion: There is no significant improvement in overall mortality, neurological outcome, or any other major clinical endpoint in adult CA patients with restrictive oxygen compared to higher oxygen therapy. Under current normothermia (36°C-37.5°C) protocols, the accumulated evidence trends toward futility for a restrictive approach, though the definitive information size has not yet been entirely accrued. Although restrictive levels could lead to an increased number of ventilator-free days, there will be an increased risk of hypoxemia.