Hypertonic Saline Versus Mannitol for ICP Reduction  


  1. Elevated intracranial pressure (ICP) is caused by excess volume in the cerebral spaces, which causes a reduction in the cerebral perfusion pressure and affects blood flow and oxygenation to the brain.   
  2. Hyperosmolar agents (hypertonic saline and mannitol) are utilized to form a gradient across the blood-brain barrier to draw fluid from the cerebral space into the vasculature, thus reducing ICP  
  3. Mannitol was previously considered the gold standard of osmotic therapy, but hypertonic saline has proven to be at least as effective as mannitol at reducing ICP  


  Hypertonic Saline   Mannitol  
   Mechanism   Increases serum sodium levels, making it more hypertonic. Giving a bolus causes a gradient for   water to follow sodium extracellularly and move out   of the cerebral spaces into the vasculature, while a   continuous infusion aids in resuscitation   Osmotic diuretic by increasing the osmolality of the glomerular filtrate, thus blocking reabsorption of water and excretion of sodium. This leads to   movement of water to extracellular and vascular   spaces and reducing the ICP  
Dose  3 – 23.4% available      3%: optimal dose is unclear, reasonable to start with   300-500mL bolus or continuous infusion at 100mL/hr and titrate per response      23.4% : 0.43-0.5 mL/kg IV bolus, max 30mL/dose  5 – 25% solutions available (20% most common)      0.25 – 1g/kg/dose IV bolus q 6-8 hours (Usually 25-100g per dose)  
Administration  3% intermittent bolus or continuous infusion   *strong osmotic gradient not retained with continuous infusions      23.4% intermittent bolus over 15 minutes  Intermittent IV infusion over 30 minutes   
Adverse Effects  Hypervolemia,  respiratory distress, electrolyte imbalances (hypernatremia)  Hypotension, hypovolemia, AKI, electrolyte disturbances (specifically K+), extravasation  
Cautions/Pearls     Solutions > 3-5% require a central line      Requires in-line filter due to risk of crystallization Avoid in hypovolemia and anuria  
Patient population to consider use in  Hypovolemic, hypotensive, traumatic resuscitation   Euvolemia, hypertensive, fluid restrictions   
Monitoring  Serum sodium 145-155mEq/dL    Serum osmolality 300-320 mOsm/L Titrate based on ICP  Serum osmolality 300-320 mOsm/L  Titrated based on ICP  
Where to find in GHS  3% Sodium chloride – 500mL   EDZONE2, EDZONE3, ALL TRAUMA STATIONS  20% Mannitol – 500ML   EDZONE2, EDZONE3, TRAUMA-M, EDETENTION  

Considerations for Administration     

  3% Sodium Chloride  23.4% Sodium Chloride  20% Mannitol  
Vascular Access  Peripheral or central  Central ONLY  Peripheral or central  
Volume (per dose)  500mL +   ~30 mL  125 – 500 mL(20%)  
Equipment  Bolus: Infusion by gravity Continuous: IV infusion pump  Syringe pump preferred   IV infusion pump  

Overview of Evidence  

Author, year   Design/ sample   size  Intervention & Comparison  Outcome  
A. Kerwin, 2009  Retrospective analysis,  (22 patients)  HTS vs mannitol   mean ICP reduction in patients with TBI  HTS is as efficacious as mannitol, if not more so, and adds to the growing literature suggesting that HTS is an effective modality for the control of elevated ICP in patients with severe TBI  
M. Li, 2015  Meta-Analysis,    7 studies    (169 patients)  HTS vs mannitol in mean ICP reduction in patients with TBI  HTS reduces ICP more effectively than mannitol in the setting of TBI  
S. Burgess, 2016  Meta-Analysis,    7 trials    (191 patients)  HTS vs mannitol in mean ICP reduction, risk of ICP treatment  failure, mortality rates, and neurological outcomes  No statistical difference in mortality and neurological outcomes. No difference in mean reduced ICP; decreased risk of ICP treatment failure with HTS  
E. Berger- Pelleiter, 2016  Meta-Analysis,   11 studies   (1,820 patients)  HTS vs mannitol in reduction of mortality, ICP, and increasing functional outcomes  No significant reduction in mortality, no significant reduction in mean ICP, no significant difference in functional outcomes  
C.  Pasarikovski,  2017  Systematic   Review,   5 studies    (175 patients)  HTS vs mannitol in ICP reduction in aneurysmal subarachnoid hemorrhage  No difference between mannitol and 3% HTS in reducing ICP in patients with aneurysmal subarachnoid hemorrhage  
J. Gu, 2018  Mata-Analysis,   12 RCTs,    (438 patients)  HTS vs mannitol in ICP reduction, ICP control, changes in serum sodium and   osmolality, mortality,   neurological function  outcome  No difference in mean ICP reduction, neurological function, and mortality. HTS may be preferred in TBI patients with refractory intracranial hypertension  
It is essential to consider the adverse effects of each agent and the comorbidities for an individual patient rather than making a simple comparison in efficacy of hypertonic saline versus mannitol  


  • Burgess S, et al. Annals of pharmacotherapy. 2016;50(4):291-300.  
  • Li M, et al. Y, 2015. Medicine. 2015;9(4):17.  
  • Dastur C, et al. Stroke and vascular neurology. 2017;2:21-29.  
  • Kerwin A, et al. J Trauma. 2009;67:277-282.  
  • Pasarikovski C, et al. World Neurosurg. 2017;105:1-6.  
  • Gu J, et al. Neurosurg Rev. 2018;42:499.  
  • Berger-Pelleiter E, et al. CJEM. 2016;18:112–120.  
  • Farrokh S, et al. Curr opin crit care. 20119; 25:105-109.  
  • Witherspoon B, et al. Nurs Clin N Am. 2017;52:249-60.   
  • Micromedex [Electronic].Greenwood Village, CO: Truven Health Analytics. Retrieved August 12, 2019 from http://www.micromedexsolutions.com

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