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.