Quantifying the Impact of Delayed Cerebral Ischemia-Related Cerebral Infarction on Clinical Outcomes Following Aneurysmal Subarachnoid Hemorrhage

Background Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and long-term disability. Although delayed cerebral ischemia (DCI) is strongly associated with poor outcome, its contribution to in-hospital mortality and its role in mediating the effect of initial severity on functional outcome remain uncertain. We aimed to quantify DCI-attributable in-hospital mortality and its mediating role between poor admission grade and unfavorable functional outcome. Methods We conducted a prospective multicenter cohort of consecutive patients with aSAH admitted to 4 specialized centers in Brazil and Belgium between 2016 and 2023. DCI-related infarction was defined according to Vergouwen et al. The attributable fraction (AF) for in-hospital mortality was estimated by regression standardization from a multivariable logistic model. Causal mediation analysis assessed how much DCI mediated the effect of poor admission grade (World Federation of Neurosurgical Societies [WFNS] grade ≥4) on unfavorable outcome (modified Rankin Scale [mRS] score, 4–6). Results Among 1789 patients (median age, 55 years; 73% female), 439 (25%) developed DCI-related infarction and 441 (25%) died in-hospital. Vasospasm, seizures, hypertension, and higher WFNS grade were independently associated with DCI. After adjustment, the AF of in-hospital mortality attributable to DCI was 12.1% (95% CI, 7.0–17.2%; P<0.001). Unfavorable outcome occurred in 71% of patients with DCI versus 35% without DCI (P<0.001). Poor admission grade increased the absolute probability of unfavorable outcome by 35.7 percentage points, of which 2.6 were mediated through DCI (7.3% mediated; 95% CI, 3.6–12.6%). Conclusions DCI accounted for an estimated 12% of in-hospital mortality but mediated only a small fraction of the effect of poor admission grade on unfavorable functional outcome. Although DCI is potentially preventable and treatable, these estimates should be interpreted cautiously given the observational design. Prospective interventional studies are needed to determine whether preventing or mitigating DCI improves survival and functional outcomes.