Revised intracerebral hemorrhage expansion definitions: Relationship with care limitations

Abstract

Background Hematoma expansion is an important therapeutic target in intracerebral hemorrhage. Recently proposed hematoma expansion definitions have not been validated, and no previous definition has accounted for withdrawal of care. Aims To externally validate revised definitions of hematoma expansion that incorporate intraventricular hemorrhage, and to test their validity in the context of withdrawal of care. Methods We analyzed data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II trial, comparing revised definitions of hematoma expansion incorporating intraventricular hemorrhage expansion to the conventional definition of “≥6 mL or ≥33%.” Primary outcome was modified Rankin Scale of 4–6 at 90 days. We calculated the incidence, sensitivity, specificity, positive and negative predictive values, and c-statistic for all definitions of hematoma expansion. Definitions were compared using nonparametric methods. Secondary analyses were performed after removing patients with withdrawal of care. Results Primary analysis included 948 patients. Using the conventional definition, the sensitivity was 37.1% and specificity was 83.2% for the primary outcome. Sensitivity improved with all three revised definitions (53.3%, 48.7%, and 45.3%, respectively), with minimal change to specificity (78.4%, 80.5%, and 81.0%, respectively). The greatest improvement was seen with the definition “≥6 mL or ≥33% or any intraventricular hemorrhage,” with increased c-statistic from 60.2% to 65.9% ( p < 0.001). Secondary analysis excluded 46 participants who experienced withdrawal of care. The revised definitions similarly outperformed the conventional definition in this population, with the greatest improvement in c-statistic using “≥6 mL or ≥33% or any intraventricular hemorrhage” (58.1% vs. 64.1%, p < 0.001). Conclusions Revised hematoma expansion definitions incorporating intraventricular hemorrhage expansion outperformed conventional definitions for predicting poor outcome, even after accounting for care limitations.