The Effect of Mannitol in the Early Stage of Supratentorial Hypertensive Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis

Abstract

Background: Mannitol has been widely applied as a priority drug in the clinical treatment for brain edema and increased intracranial pressure after intracerebral hemorrhage. However, no consensus on the efficacy and safety of mannitol has been achieved. Our meta-analysis was conducted to assess the effect of mannitol in the early stage of supratentorial hypertensive intracerebral hemorrhage (HICH) and provided a treatment reference for clinicians.

Methods: All relevant studies on mannitol treatment of supratentorial HICH were identified from the databases including PubMed, EMBASE, Cochrane Library, VIP, CNKI, and Wan Fang. Our outcome measures included the incidence of hematoma enlargement, the neurologic function improvement rate, mortality, and the incidence of aggravated brain edema. The subgroup analysis was performed to explore the impact of study type, year of publication, intervention time, and dose on the outcome measures. Publication bias was assessed by the funnel plot.

Results: Thirty-four studies consisting of 3627 patients with supratentorial HICH were included in this study (from 2000 to 2018). Significant statistical difference was found between the mannitol and nonmannitol group in terms of all the outcome measures, including the incidence of hematoma enlargement (P < 0.00001), the neurologic function improvement rate (P < 0.00001), mortality (P < 0.00001), and the incidence of aggravated cerebral edema (P = 0.0002). In subgroup analysis, the results showed that study type and intervention time did not significantly affect the outcome measures. No significant statistical difference was found in the subgroups of publication time (after 2010) (P = 0.08) and half-dose of mannitol (P = 0.20) on mortality. In addition, the further analysis showed that whatever the dose (250 mL or 125 mL) and intervention time (<24, <12, or <6 hours), mannitol could lead to hematoma enlargement.

Conclusions: For patients without obvious symptoms of intracranial hypertension or cerebral palsy, it is not recommended to use mannitol routinely in the early stage of supratentorial HICH. More high-quality trials should be included to confirm our conclusion and to ascertain the best time and dose of mannitol to use.

Keywords: Hypertensive intracerebral hemorrhage; Mannitol; Meta-analysis.