Jay Shah, MD
Wang X, Arima H, Yang J, Zhang S, Wu G, Woodward M, et al. Mannitol and Outcome in Intracerebral Hemorrhage: Propensity Score and Multivariable Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 Results. Stroke. 2015

Mannitol is an intravascular osmotic agent that reduces cerebral edema, thereby decreasing intracranial pressure. It is frequently used in malignant ischemic strokes and also recommended in intracerebral hemorrhage (ICH). However, in the latter, the magnitude of potential benefit remains uncertain. In this study, the authors hypothesized that mannitol would improve clinical outcomes in severe ICH. They analyzed data from Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). 

INTERACT2 was an international, randomized control trial that included 2839 patients with spontaneous ICH with elevated blood pressure who were assigned to either intensive blood pressure control (systolic < 140mmHg within 1 hour) or guideline-recommended control (systolic < 180mmHg). Data on any use of mannitol within 7 days of ICH were recorded. Propensity score and multivariable analysis were performed to investigate a potential relationship between mannitol and primary outcome, defined as death or major disability at 90 days. In total, there were 1533 patients treated with mannitol versus 993 who did not receive mannitol therapy. 

Overall, there was no significant difference in primary outcome. There was an apparent benefit of mannitol in patients with large hematomas (>15ml), however, this finding did not remain consistent across other cut-off points suggesting the finding was spurious. This result was in agreement with prior smaller observational and randomized control trial data. However, an analytical approach to this study is a limitation as INTERACT2 was not designed to evaluate use of mannitol. Thus, there was great variability in dose and duration of therapy. Authors attempted to account for such variability using statistical methods, but it is likely confounding variables were nonetheless present. Furthermore, patients with large hematomas or requiring early surgery were excluded from INTERACT2. Such patients would have higher intracranial pressures and presumably mannitol would have the most benefit. Further studies can evaluate mannitol treatment in this population.