Cardiac Safety and Hemodynamic Effects of Mannitol Compared with Hypertonic Saline in Intracranial Hypertension: A Systematic Review and Meta-analysis
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Background
Mannitol is widely used for reducing intracranial pressure (ICP), yet concerns persist regarding its cardiovascular safety. This systematic review and meta-analysis evaluated cardiac adverse events and mortality associated with mannitol compared with hypertonic saline (HS) in adults with intracranial hypertension.
Methods
Following PRISMA 2020, nine studies (five RCTs, two cohorts, one open-label trial, and one case-control study; n = 428) comparing mannitol with HS or standard ICP therapy were analyzed. Random-effects models generated pooled risk ratios for cardiac events and mortality. Risk of bias was assessed using JBI tools.
Results
Mannitol consistently reduced ICP by 20–35% within 30 minutes and caused only transient decreases in MAP (5–8 mmHg). Cardiac adverse events did not increase significantly (RR 1.77; 95% CI 0.00–6.3×10⁵; p = 0.67; I² = 42.5%). Mortality analysis (four studies, n = 150) showed a non-significant numerical elevation (RR 3.6; 95% CI 0.83–15.6; p = 0.06), driven mainly by one small outlier trial. Electrolyte shifts and QTc changes were more closely linked to hyperosmolality than to the specific agent used.
Conclusion
Mannitol is effective for ICP reduction without significant increases in cardiac or mortality risk compared with HS. Cardiac vulnerability appears exposure-dependent, reinforcing the need for conservative serum osmolality targets (<320 mOsm/kg), osmolar-gap monitoring, and structured ECG and electrolyte surveillance. Larger multicenter trials with standardized cardiac endpoints are required.
