Objective: Despite clinical use spanning 50+ years, questions remain concerning the optimal use of mannitol. The published reviews with meta-analysis frequently focused on mannitol's effects on a specific physiological aspect such as intracranial pressure (ICP) in sometimes heterogeneous patient populations. A comprehensive review of mannitol's effects, as well as side effects, is needed. Methods: The databases Medline (OvidSP), Embase (OvidSP), and NLM PubMed were systematically searched for randomized controlled trials (RCTs) comparing mannitol to a control therapy in either the critical care or perioperative setting. Meta-analysis was performed when feasible to examine mannitol's effects on outcomes, including ICP, cerebral perfusion pressure, mean arterial pressure (MAP), brain relaxation, fluid intake, urine output, and serum sodium. Systematic literature search was also performed to understand mannitol-related complications. Results: In total 55 RCTs were identified and 7 meta-analyses were performed. In traumatic brain injury, mannitol did not lead to significantly different MAP (SMD [95% confidence interval], CI)=−3.3 [−7.9, 1.3] mm Hg; P=0.16) but caused significantly different serum sodium concentrations (SMD [95% CI]=−8.0 [−11.0, −4.9] mmol/L; P
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