Evaluation of Complications Associated with Hypertonic Saline versus Mannitol in the Management of Intracranial Hypertension and Their Mitigation Strategies: A Systematic Review

TitleEvaluation of Complications Associated with Hypertonic Saline versus Mannitol in the Management of Intracranial Hypertension and Their Mitigation Strategies: A Systematic Review BackgroundIntracranial hypertension (ICH) worsens outcomes in patients with traumatic brain injury (TBI) or post- neurosurgical conditions. Hyperosmolar agents, particularly mannitol and hypertonic saline (HTS), are widely used to reduce intracranial pressure (ICP), but their safety profiles remain debated. This systematic review aimed to compare complications and mitigation strategies associated with mannitol and HTS in managing elevated ICP. MethodsEligible 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. 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 and ROBINS-I tools. Due to heterogeneity in design and outcomes, a narrative synthesis was performed. ResultsSeven studies (3 RCTs, 4 observational) involving 14,367 patients were included. 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. Evidence certainty ranged from low to moderate, with risk of bias and small sample sizes affecting confidence. DiscussionHTS 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. For Iranian neurosurgical centers, where ICU bed shortages and cost constrains are prevalent, HTSs renal safety profile and reduced cardiac strain in elderly patients could optimize resource utilization, a consideration absent in Western guidelines. FundingNo external funding was declared for this review.