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Hypertonic Saline Versus Mannitol for ICP Reduction  

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Introduction  

  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  

Pharmacology  

   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  

References

  • 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