Timing of Treatment and Long-Term Outcomes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Multicenter Analysis

Poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grades IV-V on admission, is associated with high mortality and disability. Although treatment initiation within 72 h is commonly recommended, the differential efficacy of specific subintervals during this therapeutic window (e.g., < 12 h, 12-24 h, and 24-72 h) has not been established. This study aims to determine the optimal timing of treatment of poor-grade aSAH using a large multicenter cohort.

This cohort study included 990 cases of poor-grade (defined as WFNS grades IV-V on admission) aSAH identified retrospectively across 12 centers. Patients were classified into three different treatment time windows: < 12 h (n = 320), 12-23 h (n = 220), and ≥ 24 h (n = 450) after symptom onset. Outcomes included mortality, unfavorable outcome (modified Rankin scale [mRS] scores 3-6), and dependency (mRS scores 3-5) at follow-up. Cox proportional hazards regression models and competing risk analyses were used to assess the association between treatment delay and outcomes.

During a median follow-up of 34.3 months, mortality rates were 46.6% for < 12 h, 38.2% for 12-23 h, and 32.4% for ≥ 24 h. Cox regression analysis revealed that treatment delays of 12-23 h (adjusted hazard ratio 0.73, 95% confidence interval 0.55-0.95) and ≥ 24 h (adjusted hazard ratio 0.64, 95% confidence interval 0.51-0.81) were associated with lower all-cause mortality compared to treatment within 12 h. Additionally, treatment delay of ≥ 24 h was associated with lower aSAH-related mortality (adjusted hazard ratio 0.62, 95% confidence interval 0.47-0.81). No significant association was found for aSAH-unrelated mortality. These findings were consistent across various patient characteristics in subgroup analyses.

Our findings indicate that treatment delay of less than 12 h after symptom onset was associated with increased mortality risk and exacerbated long-term clinical outcomes in patients with poor-grade aSAH in contemporary practice. However, the lack of control groups limits the generalizability of these data to clinical practice. Future prospective studies are warranted to confirm these results.