JMIR Publications

Background:

Intracranial hypertension (ICH) is a build-up of pressure around the brain. ICH worsens outcomes in patients with traumatic brain injury (TBI) or post-craniotomy conditions. Hyperosmolar agents, particularly mannitol and hypertonic saline (HTS), are widely used to reduce intracranial pressure (ICP), but their safety profiles is not clear.

Objective:

This systematic review aimed to compare complications and mitigation strategies associated with mannitol and HTS in managing elevated ICP.

Methods:

Eligible studies included randomized controlled trials (RCTs), cohort, and case-control studies from 2020 onward that reported complications related to mannitol or HTS in TBI or post-craniotomy patients of all ages. Non-English studies, Animal studies and studies before 2020 were excluded. A comprehensive search was conducted in PubMed, Scopus, and Web of Science (last search February 17, 2025). Risk of bias was assessed using the Cochrane ROB2 for RCTs and ROBINS-I for observational studies. Certainty of evidence as evaluated using GRADE. Due to heterogeneity in design and outcomes, a narrative synthesis was performed. Studies were grouped based on complications domain and within each domain they were compared then results were summarized descriptively.

Results:

Seven studies (3 RCTs, 4 observational) involving 14,367 patients were included. One RCT included adult patients undergoing craniotomy and another one included elderly patients with the same procedure. The third RCT included adult patients with raised ICP due to severe TBI. In observational studies, two studies included adult patients with TBI, one of them evaluated adult participants undergoing brain tumor resection and one included pediatric patients diagnosed with TBI. For brain tumor HTS was associated with fewer complications including reduced risks of electrolyte imbalance, acute kidney injury (AKI), and hemodynamic instability compared to mannitol. Mannitol was linked to hyponatremia, hypotension, and transient reductions in cardiac output, particularly in elderly or renally impaired patients. Mortality and ICU stay duration were generally comparable, though HTS showed potential ICU survival benefit.

Conclusions:

HTS may offer a safer alternative to mannitol in patients at risk of renal or cardiac complications, with similar efficacy in ICP control. Mannitol remains effective but requires intensive monitoring. These findings support tailored use based on patient comorbidities and hemodynamic stability. The study findings are limited by heterogeneity of included studies, exclusion of non-English studies, small sample size of some RCTs , potential bias in observational studies and small number of included studies.

Clinicaltrial: