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

Sep 30, 2026

Neuroprotective benefit of normobaric hyperoxia (NBHO) for acute ischemic stroke (AIS) remains uncertain. This systematic review and meta-analysis evaluated safety and functional outcomes of NBHO in adult AIS patients using randomized controlled trials. Searches covered major databases up to November 13, 2025, comparing NBHO (≥2 hours within 24 hours of onset) with room air or low-flow oxygen. Eight RCTs (n=804) assessed functional independence, disability, early recovery, and safety, showing improved outcomes without increased symptomatic intracranial hemorrhage.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Summary

Methods

Outcomes

Findings

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Funding

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Evidence before this study

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Implications of all the available evidence

Articles Efficacy and safety of normobaric hyperoxia for acute ischemic stroke: a systematic review and meta-analysis of randomized controlled trials Qin Chen, Zhuoxi Wu, Feng Chen, Jingyun Wang, Xinming Ye, and Hong Li∗ Department of Anesthesiology, Second Affiliated Hospital of Army Medical University, PLA, 83 Xinqiao Main Street, Shapingba District, Chongqing, 400037, China Summary Background 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. Methods 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) . Findings 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. Interpretation 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. Funding 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) . Copyright © 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)). Keywords: Normobaric hyperoxia; Acute ischemic stroke; Endovascular therapy; Meta-analysis Introduction Stroke is a leading cause of death and disability worldwide, with incidence rising sharply over the past decade.1 By 2050, it is projected to rank among the top three contributors to the global burden of disease, posing a critical concern for public health.2 Acute ischemic stroke (AIS) accounts for approximately 88% of all stroke cases.3 In AIS, timely revascularization through rapid restoration of cerebral blood flow can effectively rescue the ischemic penumbra, a region of eClinicalMedicine 2026;91: 103701 Published Online xxx [https://doi.org/10](https://doi.org/10) . 1016/j.eclinm.2025 . 103701 *Corresponding author. E-mail address: [lh78553@tmmu.edu.cn](lh78553@

FAQs

What clinical question does this systematic review address?

It assesses the efficacy and safety of normobaric hyperoxia (NBHO) for acute ischemic stroke, focusing on functional outcomes and adverse events.

How were eligible trials selected and what was the main outcome?

Randomized controlled trials in adults with AIS were included if NBHO was given for ≥2 hours within 24 hours of onset. The primary outcome was functional independence at three months, defined as modified Rankin Scale (mRS) 0–2.

What safety results were reported for NBHO?

NBHO did not increase the risk of symptomatic intracranial hemorrhage (sICH). Mortality at three months was lower in NBHO groups, and pneumonia risk was not increased among patients receiving endovascular therapy.

Sep 30, 2026

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