A Systematic Review of Comparing the Effect of Hypertonic Saline and Mannitol on Brain Relaxation in Supratentorial Tumor Craniotomies.

Abstract

Abstract

Introduction: Brain relaxation (BR) is essential during craniotomies to facilitate surgery and provide better patient outcomes. Hyperosmolar therapy with hypertonic saline (HTS) and mannitol (MAN) is a common intervention used to induce BR; however, it is unclear which one is more effective in supratentorial tumor craniotomies. Thus, this study aimed to perform a systematic review to provide a comprehensive update of the BR effect of HTS and MAN in supratentorial tumor craniotomies.

Methods: A PubMed search was performed up to June 20, 2025, in addition to a hand search. Only randomized controlled trials (RCTs) that compared BR measured by a 4-point scale between intravenous HTS and MAN in adult patients undergoing craniotomy for supratentorial tumors were included. The primary outcome was BR, while the secondary outcome was intracranial pressure (ICP). One reviewer screened and assessed the studies for eligibility from both the PubMed and hand searches. One reviewer extracted data on the RCTs' characteristics, methods of outcome measurement, and outcome results. Risk of bias assessment was applied to all included RCTs by the Cochrane Risk of Bias 2 tool. Data were presented in graphs, and qualitative analysis was performed on all outcomes.

Results: A total of 8 RCTs and 513 analyzed participants were included in this systematic review. 5 RCTs had low risk of bias, while 2 RCTs had some concerns. All included RCTs investigated BR. In terms of statistical significance, 5 RCTs concluded no statistical difference between the BR effect of HTS and MAN, 1 RCT found that HTS was significantly more effective, and 2 RCTs involved a third group, which made the extraction of a firm conclusion challenging. Common trends were observed in most RCTs, including the higher scoring in (grades 1 and 2) compared to (grades 3 and 4) for both hyperosmolar agents; the highest scoring for HTS was in grade 1, while the highest scoring for MAN was in the less BR (grade 2) most of the time; the HTS group had higher scoring in grade 1 than MAN most of the time; and HTS was lower than MAN in the worst BR grade 4 most of the time. 2 RCTs only investigated ICP. 1 RCT suggested no significant difference between HTS and MAN in lowering ICP, while the other RCT found that HTS was significantly better.

Conclusion: Despite the lack of a statistically significant difference in the BR effect between HTS and MAN, the common superiority trends of HTS raised the possibility of a statistically significant HTS superiority and the need for an updated meta-analysis. Firm conclusions were not possible regarding ICP, and more trials need to be conducted in the future.