Supplementary Material for: Normobaric Oxygen Therapy in Acute Stroke: A Systematic Review and Meta-Analysis

<b><i>Purpose:</i></b> Normobaric oxygen (NBO) is potentially a readily accessible neuroprotective therapy. We undertook a systematic review to assess NBO in acute stroke. <b><i>Methods:</i></b> MEDLINE, EMBASE, and CENTRAL databases were searched to December 2020. Randomized controlled trials of NBO administered &lt;7 days after stroke to normoxic patients with no other indication for oxygen were identified. Data on early neurological recovery; functional outcome; mortality; oxygen saturation, and imaging markers were collected. <b><i>Findings:</i></b> Fifteen publications involving 12 cohorts and 9,255 participants were identified. One study with 8,003 participants had low risk of bias, but the designs of smaller trials had limitations. Ninety-seven per cent of participants were in studies of low-flow oxygen (≤4 L/min). 82.8% had ischaemic stroke. Median time to treatment was 19.3 h. Meta-analysis demonstrated no significant effect on: reduction in National Institutes of Health Stroke Scale at 7 days in all stroke or ischaemic stroke only (mean difference −0.16 [−1.11 to 0.80] and −0.73 [−3.54 to 2.08], respectively); modified Rankin scale at 3–6 months of follow-up (combined standardized mean difference [SMD] −0.08 [−0.38 to 0.22]; 3 months SMD −0.01 [−0.03 to 0.029]; 6-month SMD −0.20 [−1.49 to 1.09]), or mortality (odds ratio 1.15 [0.87–1.53]). <b><i>Discussion:</i></b> The majority of patients were administered low-flow oxygen in the sub-acute phase. Intervention strategies targeted at modification of early tissue survival (higher oxygen delivery and administration at early time points when significant volumes of viable tissue persist) have not been tested adequately. <b><i>Conclusion:</i></b> Studies of NBO have shown no significant effect on early neurological recovery, functional outcome, or mortality in acute stroke. Oxygen has been predominantly low-flow and commenced in the sub-acute phase.