Hyperbaric oxygen therapy timing, early neurohemodynamic response and functional outcome in acute ischemic stroke

The optimal timing of HBOT initiation after AIS remains uncertain, particularly in relation to early cerebral hemodynamic responses and subsequent functional outcome. The present study determined whether hyperbaric oxygen therapy (HBOT) initiation timing was associated with early neurohemodynamic response and 90-day functional outcome among patients with acute ischemic stroke (AIS) who received HBOT within 72 h of symptom onset. In the present single-center, retrospective, exposure-stratified cohort study, patients were grouped according to HBOT initiation at <24 h, 24 to <48 h or 48 to 72 h following symptom onset. No non-HBOT comparator was included. The primary outcome was favorable functional status at 90 days, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary analyses assessed early transcranial Doppler (TCD)-defined hemodynamic response, early neurological response, ordinal 90-day mRS shift, an exploratory treatment-emergent integrated early neurohemodynamic response phenotype and safety. Multivariable logistic regression, ordinal logistic regression and robustness analyses used the 48 to 72 h window as the reference. Among the 429 patients, HBOT initiation at <24 h (odds ratio (OR)=2.68; 95% CI, 1.55-4.63; P<0.001) and 24 to <48 h (OR=1.72; 95% CI, 1.04-2.82; P=0.033) was associated with greater odds of a favorable 90-day functional outcome than initiation at 48 to 72 h. Both earlier windows were also associated with greater odds of a lower 90-day mRS category (common OR=2.44; 95% CI, 1.53-3.88; P<0.001; common OR=1.68; 95% CI, 1.09-2.57; P=0.017). TCD hemodynamic response was more frequent in both earlier windows (P<0.001 and P=0.043), whereas a higher rate of early neurological response and a lower rate of early neurological deterioration were observed only in the <24 h window (P=0.003 and P=0.025, respectively). The exploratory integrated early neurohemodynamic response phenotype was associated with favorable functional outcome at 90 days (OR=2.95; 95% CI, 1.76-4.92; P<0.001). Safety outcomes did not differ significantly across initiation windows. Among HBOT-treated patients with AIS, earlier initiation was associated with more favorable early neurohemodynamic and neurological responses and improved 90-day functional outcomes, without evidence of increased safety events. As the present observational study included no non-HBOT comparator, the present findings do not establish HBOT efficacy relative to standard care without HBOT or a causal benefit of earlier initiation. Residual confounding and treatment-selection bias remain possible.