All Pharmacy Pearls

Introduction

  • 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.

  • 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

  • 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

Clinical Detail

Hypertonic SalineMannitol
MechanismIncreases 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 resuscitationOsmotic 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
Dose3 – 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)
Administration3% 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 EffectsHypervolemia, respiratory distress, electrolyte imbalances (hypernatremia)Hypotension, hypovolemia, AKI, electrolyte disturbances (specifically K+), extravasation
Cautions/PearlsSolutions > 3-5% require a central lineRequires in-line filter due to risk of crystallization
Avoid in hypovolemia and anuria
Patient population to consider use inHypovolemic, hypotensive, traumatic resuscitationEuvolemia, hypertensive, fluid restrictions
MonitoringSerum sodium 145-155mEq/dL
Serum osmolality 300-320 mOsm/L
Titrate based on ICP		Serum osmolality 300-320 mOsm/L
Titrated based on ICP
3% Sodium Chloride23.4% Sodium Chloride20% Mannitol
Vascular AccessPeripheral or centralCentral ONLYPeripheral or central
Volume (per dose)500mL +~30 mL125 – 500 mL (20%)
EquipmentBolus: Infusion by gravity
Continuous: IV infusion pump		Syringe pump preferredIV infusion pump

Evidence

Author, yearDesign/ sample sizeIntervention & ComparisonOutcome
A. Kerwin, 2009Retrospective analysis, (22 patients)HTS vs mannitol mean ICP reduction in patients with TBIHTS 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, 2015Meta-Analysis, 7 studies (169 patients)HTS vs mannitol in mean ICP reduction in patients with TBIHTS reduces ICP more effectively than mannitol in the setting of TBI
S. Burgess, 2016Meta-Analysis, 7 trials (191 patients)HTS vs mannitol in mean ICP reduction, risk of ICP treatment failure, mortality rates, and neurological outcomesNo statistical difference in mortality and neurological outcomes. No difference in mean reduced ICP; decreased risk of ICP treatment failure with HTS
E. Berger-Pelleiter, 2016Meta-Analysis, 11 studies (1,820 patients)HTS vs mannitol in reduction of mortality, ICP, and increasing functional outcomesNo significant reduction in mortality, no significant reduction in mean ICP, no significant difference in functional outcomes
C. Pasarikovski, 2017Systematic Review, 5 studies (175 patients)HTS vs mannitol in ICP reduction in aneurysmal subarachnoid hemorrhageNo difference between mannitol and 3% HTS in reducing ICP in patients with aneurysmal subarachnoid hemorrhage
J. Gu, 2018Meta-Analysis, 12 RCTs, (438 patients)HTS vs mannitol in ICP reduction, ICP control, changes in serum sodium and osmolality, mortality, neurological function outcomeNo difference in mean ICP reduction, neurological function, and mortality. HTS may be preferred in TBI patients with refractory intracranial hypertension

Conclusions

  • Both hypertonic saline and mannitol are hyperosmolar agents that create an osmotic gradient across the blood-brain barrier to draw fluid out of the cerebral space and reduce elevated intracranial pressure.
  • Mannitol was historically the gold standard, but hypertonic saline has been shown to be at least as effective at reducing ICP, and across the meta-analyses summarized here the two agents show no consistent difference in mortality or neurological outcomes.
  • Agent selection is driven by the patient’s volume status: hypertonic saline favors the hypovolemic or hypotensive trauma-resuscitation patient, while mannitol suits the euvolemic or hypertensive patient and those needing fluid restriction, with 23.4% saline requiring central access.

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

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