Hypertonic Saline vs Mannitol for ICP — Pharmacy Pearl | PACU

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 are the cornerstone of acute ICP management.

Key Concepts

Hyperosmolar agents (hypertonic saline and mannitol) form a gradient across the blood-brain barrier to draw fluid from cerebral space into the vasculature, reducing ICP
Mannitol was previously considered the gold standard of osmotic therapy
Hypertonic saline has proven to be at least as effective as mannitol at reducing ICP

Pharmacology Comparison

Parameter	Hypertonic Saline	Mannitol
Mechanism	Increases serum sodium levels, creating a gradient for water to follow sodium extracellularly and move out of cerebral spaces into the vasculature. Continuous infusion aids in resuscitation.	Osmotic diuretic — increases osmolality of glomerular filtrate, blocking reabsorption of water and causing excretion of sodium. Moves water to extracellular and vascular spaces.
Dose	3%: 300–500 mL bolus or continuous infusion at 100 mL/hr, titrate per response 23.4%: 0.43–0.5 mL/kg IV bolus, max 30 mL/dose	20% (most common): 0.25–1 g/kg/dose IV bolus q6–8h (Usually 25–100 g per dose)
Administration	3% intermittent bolus or continuous infusion *Strong osmotic gradient not retained with continuous infusions 23.4% intermittent bolus over 15 min	Intermittent IV infusion over 30 minutes
Adverse Effects	Hypervolemia Respiratory Distress Hypernatremia	Hypotension AKI Hypovolemia K+ Disturbances Extravasation
Cautions/Pearls	Solutions >3–5% require a central line	Requires in-line filter due to risk of crystallization Avoid in hypovolemia and anuria
Population	Hypovolemic Hypotensive Traumatic Resuscitation	Euvolemia Hypertensive Fluid Restrictions
Monitoring	Serum Na: 145–155 mEq/dL Serum osmolality: 300–320 mOsm/L Titrate based on ICP	Serum osmolality: 300–320 mOsm/L Titrate based on ICP

Clinical Pearl

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.

Considerations for Administration

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

Parameter

3% Sodium Chloride

23.4% Sodium Chloride

20% Mannitol

Vascular Access

Peripheral or Central

Central ONLY

Peripheral or Central

Volume (per dose)

500 mL+

~30 mL

125–500 mL

Equipment

Bolus: Infusion by gravity

Continuous: IV infusion pump

Syringe pump preferred

IV infusion pump

Overview of Key Evidence

7 Studies

Author / Year	Design (n)	Intervention	Key Findings
Kerwin, 2009¹	Retrospective n=22	HTS vs mannitol — mean ICP reduction in patients with TBI	HTS at least as efficacious as mannitol Adds to growing literature supporting HTS for elevated ICP in severe TBI
Li, 2015²	Meta-Analysis 7 studies, n=169	HTS vs mannitol in mean ICP reduction in TBI	HTS reduces ICP more effectively than mannitol in TBI
Burgess, 2016³	Meta-Analysis 7 trials, n=191	HTS vs mannitol — mean ICP reduction, treatment failure risk, mortality, neurological outcomes	No statistical difference in mortality/neuro outcomes Decreased ICP treatment failure with HTS
Berger-Pelleiter, 2016⁴	Meta-Analysis 11 studies, n=1,820	HTS vs mannitol — mortality, ICP reduction, functional outcomes	No significant reduction in mortality No significant difference in functional outcomes
Pasarikovski, 2017⁵	Systematic Review 5 studies, n=175	HTS vs mannitol in ICP reduction in aneurysmal subarachnoid hemorrhage	No difference in ICP reduction in aSAH
Gu, 2018⁶	Meta-Analysis 12 RCTs, n=438	HTS vs mannitol — ICP reduction, ICP control, serum Na/osmolality changes, mortality, neurological function	No difference in ICP, neuro function, mortality HTS may be preferred in refractory intracranial HTN

Clinical Conclusions

Bottom Line

Hypertonic saline has proven to be at least as effective as mannitol at reducing ICP. The choice between agents should be guided by individual patient factors rather than a simple efficacy comparison.

HTS and mannitol are both effective hyperosmolar agents for ICP reduction with no significant differences in mortality or neurological outcomes.

HTS may have an advantage in TBI patients with refractory intracranial hypertension and may reduce ICP treatment failure rates.

Consider patient comorbidities and volume status when selecting an agent: HTS for hypovolemic/hypotensive patients; mannitol for euvolemic/hypertensive patients with fluid restrictions.

Monitor serum osmolality (300–320 mOsm/L) and titrate based on ICP for both agents.

Full Reference List

10 refs

Burgess S, et al. Annals of Pharmacotherapy. 2016;50(4):291–300.
Li M, et al. 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. 2019;25:105–109.
Witherspoon B, et al. Nurs Clin N Am. 2017;52:249–60.
Micromedex [Electronic]. Greenwood Village, CO: Truven Health Analytics.

Hypertonic Saline Versus Mannitol for ICP Reduction