Association of Impaired Hematoma Clearance After Aneurysmal Subarachnoid Hemorrhage with Delayed Cerebral Ischemia, Hydrocephalus, and Long-Term Outcomes

OBJECTIVE: Although delayed cerebral ischemia (DCI) and hydrocephalus contribute to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH), it remains unclear whether improved subarachnoid hematoma clearance translates into better long-term outcomes and through which mechanisms. We investigated the association between hematoma clearance and long-term outcomes and quantified the mediating effects of DCI and shunt-dependent hydrocephalus. METHODS: We retrospectively analyzed patients with aSAH who underwent aneurysmal clipping between April 2012 and March 2024 at a single center. Hematoma burden was assessed using the Hijdra sum score (HSS). Hematoma clearance was defined as the percentage reduction in HSS between admission and days 7‒10 and dichotomized using the median (91.5%). Poor outcome was defined as a modified Rankin Scale (mRS) score ≥ 3 at 6 months. Multivariate logistic regression analyses and causal mediation analyses were performed to assess direct and indirect effects of hematoma clearance on long-term outcomes mediated by DCI and shunt-dependent hydrocephalus. RESULTS: A total of 442 patients were included. Poor hematoma clearance was independently associated with poor 6-month outcomes [odds ratio (OR) 2.32, p = 0.003], DCI (OR 1.83, p = 0.025), and shunt-dependent hydrocephalus (OR 2.55, p < 0.001). Mediation analysis showed that shunt-dependent hydrocephalus mediated approximately 22% of the total effect of poor clearance on poor outcome [average causal mediation effect (ACME) 0.035, p < 0.001], whereas mediation via DCI was smaller and did not reach statistical significance (ACME 0.020 p = 0.078). A substantial direct effect independent of these mediators was observed. CONCLUSIONS: Poor hematoma clearance after aSAH is associated with worse long-term outcomes, partly mediated by shunt-dependent hydrocephalus and to a lesser extent by DCI. However, a large proportion of the effect appears to be independent of these pathways, suggesting the involvement of additional mechanisms beyond DCI and hydrocephalus.