Efficacy and safety of normobaric hyperoxia for acute ischemic stroke: a systematic review and meta-analysis of randomized controlled trials.

Abstract

The neuroprotective effects of normobaric hyperoxia (NBHO) for treating acute ischemic stroke (AIS) remain unclear. This systematic review and meta-analysis evaluated the safety and functional outcomes of NBHO in AIS patients. We searched major databases until November 13, 2025, for randomized controlled trials (RCTs) comparing NBHO (≥2 h within 24 h of onset) with room air or low-flow oxygen in adult patients with AIS. Two reviewers independently screened studies, with disagreements resolved by a third reviewer. The primary outcome was functional independence (modified Rankin Scale [mRS] scores 0-2) at three months. Secondary outcomes included reduced disability (ordinal shift across mRS grades 0-6), early neurological recovery (changes in National Institutes of Health Stroke Scale [NIHSS] within 7 days), and infarct volume changes. Safety outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH), and pneumonia. Outcomes eligible for meta-analysis were analyzed using a random-effects model (Paule-Mandel heterogeneity estimation) with Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment for the primary analysis and without HKSJ adjustment for secondary analysis. Registration: PROSPERO (CRD42024584308). Eight RCTs involving 804 participants were included. Six studies (n = 746) showed that NBHO improved functional independence (RR 1.28, HKSJ 95% CI 1.07-1.51; <i>P</i> = 0.015), reduced disability (cOR 1.72, HKSJ 95% CI 1.35-2.20; <i>P</i> = 0.002), and lowered mortality (RR 0.62, HKSJ 95% CI 0.39-0.99; <i>P</i> = 0.047) at three months. NBHO also decreased NIHSS scores at 72 h (MD -2.18, HKSJ 95% CI -3.45 to -0.90; <i>P</i> = 0.009) across five studies, though effects at other timepoints were significant only in secondary analysis. NBHO did not increase the risk of sICH (RR 0.79, HKSJ 95% CI 0.45-1.40; <i>P</i> = 0.347). Among patients receiving endovascular therapy (five studies), NBHO did not increase the risk of pneumonia (RR 0.97, HKSJ 95% CI 0.61-1.55; <i>P</i> = 0.863). Results for infarct volume and subgroup analyses were inconclusive due to limited data. In this meta-analysis of predominantly Chinese populations, NBHO may improve functional independence, reduce disability, and lower mortality at three months, and promote early neurological recovery at 72 h without compromising safety. Generalizability to other ethnic groups requires confirmation. This work is supported by the Cultivation Program of Clinical Research Special Project of The Second Affiliated Hospital of Army Medical University (Grant No. 2024F037).