Efficacy and safety of hypertonic saline versus mannitol in the acute management of traumatic brain injury in the emergency department: a systematic review
DOI:
https://doi.org/10.65759/skyq2a03Keywords:
Traumatic brain injury, Hypertonic saline, Mannitol, Intracranial pressure, Cerebral perfusion pressure, OsmotherapyAbstract
Background: Hypertonic saline (HTS) and mannitol are used widely for raised intracranial pressure (ICP) after traumatic brain injury (TBI), but the preferred agent remains uncertain. This systematic review evaluated the efficacy and safety in acute TBI management. Methods: This review followed PRISMA principles. PubMed, Embase, Scopus, and Web of Science were searched for original studies comparing HTS or related hyperosmolar sodium solutions with mannitol in TBI. Eligible designs included randomized trials, prospective studies, retrospective cohorts, case-control studies, and multicenter observational studies. Outcomes included ICP reduction, cerebral perfusion pressure, neurological outcome, mortality, treatment failure, and adverse effects. Results: Thirteen original studies were included, most enrolled severe TBI patients with raised ICP. Both agents reduced ICP. Several studies reported physiological advantages with HTS, including lower ICP burden, improved cerebral perfusion pressure, better brain tissue oxygenation, faster target achievement, or lower treatment failure. Studies using similar osmotic burdens found comparable short-term ICP reduction. HTS increased serum sodium or osmolality in some studies, and mannitol was associated with greater urine output. Conclusion: HTS had physiological advantages, and the included studies does not prove better clinical outcome than mannitol.
References
Maas AIR, Menon DK, David Adelson PD, Andelic N, Bell MJ, Belli A, et al. Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research. Lancet Neurol 2017;16:987–1048. https://doi.org/10.1016/S1474-4422(17)30371-X.
[2] James SL, Bannick MS, Montjoy-Venning WC, Lucchesi LR, Dandona L, Dandona R, et al. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019;18:56–87. https://doi.org/10.1016/S1474-4422(18)30415-0.
[3] Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg 2019;130:1080–97. https://doi.org/10.3171/2017.10.JNS17352.
[4] Wakai A, Mccabe A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database of Systematic Reviews 2013;2013. https://doi.org/10.1002/14651858.CD001049.pub5.
[5] Cook AM, Morgan Jones G, Hawryluk GWJ, Mailloux P, McLaughlin D, Papangelou A, et al. Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients. Neurocrit Care 2020;32:647–66. https://doi.org/10.1007/s12028-020-00959-7.
[6] Tatro HA, McMillen JC, Hamilton LA, Rowe AS. 23.4% Sodium Chloride Versus Mannitol for the Reduction of Intracranial Pressure in Patients With Traumatic Brain Injury: A Single-Center Retrospective Cohort Study. Annals of Pharmacotherapy 2021;55:988–94. https://doi.org/10.1177/1060028020982379.
[7] Patil H, Gupta R. A Comparative Study of Bolus Dose of Hypertonic Saline, Mannitol, and Mannitol Plus Glycerol Combination in Patients with Severe Traumatic Brain Injury. World Neurosurg 2019;125:e221–8. https://doi.org/10.1016/j.wneu.2019.01.051.
[8] Chong SL, Zhu Y, Wang Q, Caporal P, Roa JD, Chamorro FIP, et al. Clinical Outcomes of Hypertonic Saline vs Mannitol Treatment among Children with Traumatic Brain Injury. JAMA Netw Open 2025;8. https://doi.org/10.1001/jamanetworkopen.2025.0438.
[9] Mangat HS, Wu X, Gerber LM, Schwarz JT, Fakhar M, Murthy SB, et al. Hypertonic Saline is Superior to Mannitol for the Combined Effect on Intracranial Pressure and Cerebral Perfusion Pressure Burdens in Patients with Severe Traumatic Brain Injury. Clin Neurosurg 2020;86:221–30. https://doi.org/10.1093/neuros/nyz046.
[10] Kumar SA, Devi BI, Reddy M, Shukla D. Comparison of equiosmolar dose of hyperosmolar agents in reducing intracranial pressure-a randomized control study in pediatric traumatic brain injury. Child’s Nervous System 2019;35:999–1005. https://doi.org/10.1007/s00381-019-04121-3.
[11] Vialet R, Albanèse J, Thomachot L, Antonini F, Bourgouin A, Alliez B, et al. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med 2003;31:1683–7. https://doi.org/10.1097/01.CCM.0000063268.91710.DF.
[12] Francony G, Fauvage B, Falcon D, Canet C, Dilou H, Lavagne P, et al. Equimolar doses of mannitol and hypertonic saline in the treatment of increased intracranial pressure. Crit Care Med 2008;36:795–800. https://doi.org/10.1097/CCM.0B013E3181643B41.
[13] Ichai C, Armando G, Orban JC, Berthier F, Rami L, Samat-Long C, et al. Sodium lactate versus mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med 2009;35:471–9. https://doi.org/10.1007/s00134-008-1283-5.
[14] Oddo M, Levine JM, Frangos S, Carrera E, Maloney-Wilensky E, Pascual JL, et al. Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension. J Neurol Neurosurg Psychiatry 2009;80:916–20. https://doi.org/10.1136/jnnp.2008.156596.
[15] Cottenceau V, Masson F, Mahamid E, Petit L, Shik V, Sztark F, et al. Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury. J Neurotrauma 2011;28:2003–12. https://doi.org/10.1089/neu.2011.1929.
[16] Sakellaridis N, Pavlou E, Karatzas S, Chroni D, Vlachos K, Chatzopoulos K, et al. Comparison of mannitol and hypertonic saline in the treatment of severe brain injuries Clinical article. J Neurosurg 2011;114:545–8. https://doi.org/10.3171/2010.5.JNS091685.
[17] Mangat HS, Chiu YL, Gerber LM, Alimi M, Ghajar J, Härtl R. Hypertonic saline reduces cumulative and daily intracranial pressure burdens after severe traumatic brain injury. J Neurosurg 2015;122:202–10. https://doi.org/10.3171/2014.10.JNS132545.
[18] Van Veen E, Nieboer D, Kompanje EJO, Citerio G, Stocchetti N, Gommers D, et al. Comparative Effectiveness of Mannitol Versus Hypertonic Saline in Patients With Traumatic Brain Injury: A CENTER-TBI Study. J Neurotrauma 2023;40:1352–65. https://doi.org/10.1089/neu.2022.0465.
[19] Boone MD, Oren-Grinberg A, Robinson TM, Chen CC, Kasper EM. Mannitol or hypertonic saline in the setting of traumatic brain injury: What have we learned? Surg Neurol Int 2015;6. https://doi.org/10.4103/2152-7806.170248.
[20] Schwimmbeck F, Voellger B, Chappell D, Eberhart L. Hypertonic saline versus mannitol for traumatic brain injury: A systematic review and meta-analysis with trial sequential analysis. J Neurosurg Anesthesiol 2021;33:10–20. https://doi.org/10.1097/ANA.0000000000000644.
[21] Shi J, Tan L, Ye J, Hu L, Das UN. Hypertonic saline and mannitol in patients with traumatic brain injury: A systematic and meta-analysis. Medicine (United States) 2020;99. https://doi.org/10.1097/MD.0000000000021655.
[22] Miyoshi Y, Kondo Y, Suzuki H, Fukuda T, Yasuda H, Yokobori S, et al. Effects of hypertonic saline versus mannitol in patients with traumatic brain injury in prehospital, emergency department, and intensive care unit settings: A systematic review and meta-analysis. J Intensive Care 2020;8. https://doi.org/10.1186/s40560-020-00476-x.
[23] Chen H, Song Z, Dennis JA. Hypertonic saline versus other intracranial pressure–lowering agents for people with acute traumatic brain injury. Emergencias 2021;33:218–9. https://doi.org/10.1002/14651858.CD010904.pub3


