Abstract DP380: Normobaric Hyperoxygenation in Conjunction with Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Introduction: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. While reperfusion therapies such as intravenous thrombolysis and endovascular thrombectomy are effective in restoring cerebral blood flow, outcomes remain suboptimal in many patients. Normobaric hyperoxygenation (NBO), the administration of high-concentration oxygen via non-invasive methods, has been proposed as a neuroprotective adjunct to reperfusion therapy by preserving the ischemic penumbra. We analyzed data from all studies evaluating adjunctive NBO administered before or at the onset of reperfusion therapy in patients with AIS. Methods: We searched MEDLINE (Ovid), EMBASE (Ovid), CENTRAL, Scopus, and Web of Science from inception to June 24, 2025. The review was PROSPERO-registered (CRD420251065883) and followed PRISMA 2020 guidelines. Five studies (four randomized controlled trials and one cohort) involving 792 patients were included. Random-effects meta-analyses were conducted (reporting MDs/ORs with 95% CIs); risk of bias was assessed with RoB 2/ROBINS-I and certainty with GRADE. Primary outcomes were early neurological improvement (NIH Stroke Scale NIHSS at 24 hours and 7 days), functional outcome (modified Rankin Scale mRS at 90 days), and all-cause mortality. Secondary outcomes included infarct volume, symptomatic intracranial hemorrhage (SIH), functional independence (mRS 0-2), and treatment-related adverse events. Results: NBO was associated with a significant reduction in NIHSS scores at 24 hours (mean difference -1.45; 95% CI -2.75 to -0.16; p=0.04), reduced infarct volume within 72 hours (mean difference -17.58 mL; 95% CI -26.60 to -8.56; p=0.01), and increased odds of achieving functional independence at 90 days (OR 2.10; 95% CI 1.23 to 3.56; p=0.02). NIHSS at 7 days, 90-day mRS, and mortality showed no conclusive differences (CIs crossed the null), with point estimates favoring NBO. There was no increase in SIH or oxygen-related adverse events with NBO. Heterogeneity for significant findings was low. Conclusion: Early administration of NBO as an adjunct to reperfusion therapy in AIS may confer modest clinical benefits, including improved early neurological recovery, reduced infarct volume, and greater likelihood of functional independence, without increased risk of adverse events. Further high-quality randomized trials are needed to confirm these findings and determine the optimal protocol for NBO delivery in AIS.