Hyperosmolar therapy is regarded as the mainstay for treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI). This still has been disputed as application of hypertonic saline (HS) or mannitol for treating patients with severe TBI. Thus, this meta-analysis was performed to further compare the advantages and disadvantages of mannitol with HS for treating elevated ICP after TBI. We conducted a systematic search on PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wan Fang Data, VIP Data, SinoMed, and China National Knowledge Infrastructure (CNKI) databases. Studies were included or not based on the quality assessment by the Jadad scale and selection criteria. Twelve RCTs with 438 patients were enrolled for the meta-analysis. The comparison of HS and mannitol indicated that they were close in field of improving function outcome (RR = 1.17, 95% CI 0.89 to 1.54, p = 0.258) and reducing intracranial pressure (MD = - 0.16, 95% CI: - 0.59 to 0.27, p = 0.473) and mortality (RR = 0.78, 95% CI 0.53 to 1.16, p = 0.216). The pooled relative risk of successful ICP control was 1.06 (95% CI: 1.00 to 1.13, p = 0.044), demonstrating that HS was more effective than mannitol in ICP management. Both serum sodium (WMD = 5.30, 95% CI: 4.37 to 6.22, p < 0.001) and osmolality (WMD = 3.03, 95% CI: 0.18 to 5.88, p = 0.037) were increased after injection of hypertonic saline. The results do not lend a specific recommendation to select hypertonic saline or mannitol as a first-line for the patients with elevated ICP caused by TBI. However, for the refractory intracranial hypertension, hypertonic saline seems to be preferred.

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