Evaluation of Cardiac Complications due to Mannitol Application in Elevated Intracranial Pressure patients: A Systematic Review and Meta-analysis
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Background
Mannitol is a widely used hyperosmotic agent for intracranial pressure (ICP) control, yet its cardiovascular safety profile remains uncertain. This systematic review and meta-analysis aimed to evaluate cardiac complications and mortality associated with mannitol administration in patients with elevated ICP.
Methods
Following PRISMA 2020 guidelines, five databases (PubMed, Scopus, Web of Science, Embase, and Cochrane Library) were searched through October 2025 without language or date restrictions. Eligible studies included randomized controlled trials and cohort designs comparing mannitol with hypertonic saline (HS) or standard therapy in adult patients with intracranial hypertension. Data were pooled using random-effects models to estimate risk ratios (RR) with 95 % confidence intervals (CI) for cardiac adverse events and all-cause mortality. Risk of bias was assessed using the Joanna Briggs Institute checklists, and evidence certainty was graded with GRADE criteria.
Results
Eight studies (five RCTs, two cohort studies, one open-label trial; n = 391) met inclusion criteria. Mannitol reduced ICP by 20–35 % within 30 minutes, with only transient, clinically insignificant MAP decreases (∼5–8 mmHg). The pooled RR for cardiac adverse events was 1.77 (95 % CI 0.00– 6.3 × 10 5 ; p = 0.67; I 2 = 42.5 %), showing no significant increase in arrhythmia, hypotension, or pulmonary edema. Mortality analysis (four studies, n ≈ 150) yielded RR = 3.6 (95 % CI 0.83–15.6; p = 0.06; I 2 = 0 %), reflecting a non-significant numerical excess largely driven by a single small outlier study. Electrolyte shifts and QTc prolongation correlated with hyperosmolality rather than agent identity.
Conclusion
Current low-certainty evidence indicates that mannitol provides effective ICP reduction without significant increases in cardiac or mortality risk compared with HS. Cardiac vulnerability appears exposure-dependent, emphasizing conservative osmolality targets (< 320 mOsm/kg), osmolar-gap monitoring, and ECG/electrolyte surveillance during high-dose therapy. Large, multicenter RCTs with standardized cardiac safety endpoints are needed to strengthen these findings.
