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

## TL;DR

This study finds that breathing extra oxygen may help people recover better after a stroke without causing more harm.

## Contribution

A meta-analysis of RCTs shows normobaric hyperoxia improves outcomes in acute ischemic stroke patients.

## Key findings

- Normobaric hyperoxia improved functional independence and reduced disability in stroke patients.
- It also lowered mortality and promoted early neurological recovery without increasing safety risks.
- Results were inconclusive for infarct volume and subgroup analyses due to limited data.

## 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; P = 0.015), reduced disability (cOR 1.72, HKSJ 95% CI 1.35–2.20; P = 0.002), and lowered mortality (RR 0.62, HKSJ 95% CI 0.39–0.99; P = 0.047) at three months. NBHO also decreased NIHSS scores at 72 h (MD –2.18, HKSJ 95% CI –3.45 to −0.90; P = 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; P = 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; P = 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 10.13039/501100012397Army Medical University (Grant No. 2024F037).