Normobaric Hyperoxia Combined with Endovascular Treatment Based on Temporal Gradient: A dose-escalation study

BACKGROUND Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke (AIS). Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment (EVT). METHODS Patients with acute stroke who had an indication for EVT at Tianjin Huanhu Hospital were included and randomly assigned to four groups (1:1 ratio) based on NBO therapy duration: 1) Sham-NBO group (oxygen 1 L/min continuously for 4 h); 2) NBO-2h group (10 L/min continuously for 2 h); 3) NBO-4h group (10 L/min continuously for 4 h); and 4) NBO-6h group (10 L/min continuously for 6 h). The primary outcome was cerebral infarction volume at 72 h after randomization. The primary safety outcome was the 90-d mortality rate. RESULTS A total of 100 patients were included (Sham-NBO group, n=25; NBO-2h group, n=25; NBO-4h group, n=25; and NBO-6h group, n=25). The 72-h cerebral infarct volumes were 39.4 ± 34.3 ml, 30.6 ± 30.1ml, 19.7 ± 15.4 ml, and 22.6 ± 22.4 ml, respectively (P=0.013). The NBO-4h and NBO-6h groups exhibited significant differences compared to the Sham-NBO group (adjusted P values: 0.011 and 0.027, respectively). No significant differences were found between the NBO-4h and NBO-6h groups. The National Institute of Health Stroke Scale (NIHSS) scores at 24 h, 72 h, and 7 d, and the changes in NIHSS scores from baseline to 24 h were significantly different in the NBO-4h and NBO-6h groups compared with the Sham-NBO group (P<0.05). No significant differences were observed between the NBO-4h and NBO-6h groups in the NIHSS assessments. No significant differences were noted among groups in the 90-d mortality rate, symptomatic intracranial haemorrhage, early neurological deterioration, and severe adverse events. CONCLUSIONS The effectiveness of NBO therapy was associated with oxygen administration duration. In patients with AIS who undergone EVT, NBO treatment for 4-6 h may yield better outcomes than other oxygen therapy regimens or low flow oxygen therapy. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05404373 .