What is the role of hypertonic saline (HS) in managing intracranial pressure (ICP) in patients with intracranial hemorrhage (ICH)?

Hypertonic Saline for Intracranial Pressure Management in Intracranial Hemorrhage

Hypertonic saline is highly effective at reducing intracranial pressure in patients with intracranial hemorrhage, but it does not improve survival or neurological outcomes. 1, 2

Efficacy for ICP Reduction

Use hypertonic saline as a primary osmotic agent for elevated ICP in intracranial hemorrhage patients—it effectively reduces ICP within 10-15 minutes with effects lasting 2-4 hours. 2

• Multiple randomized controlled trials and case-control studies confirm that hypertonic saline significantly reduces ICP in patients with subarachnoid hemorrhage and other causes of intracranial hypertension 1
• In experimental ICH models, both 3% and 23.4% hypertonic saline produce immediate ICP reduction comparable to or better than mannitol 3
• Clinical studies in aneurysmal subarachnoid hemorrhage demonstrate that 3% hypertonic saline (160 mL) produces equivalent ICP reduction to 20% mannitol (150 mL) 4
• The mechanism involves creating an osmotic gradient across the blood-brain barrier, displacing water from brain tissue to the hypertonic extracellular space 2

Recommended Dosing Protocol

Administer 7.5% hypertonic saline as a 250 mL bolus over 15-20 minutes for acute ICP elevation, targeting serum sodium of 145-155 mmol/L. 2

• For bolus therapy: 7.5% saline at 2 mL/kg body weight (typically 250 mL) infused at 20 mL/min produces maximum effect at 98 minutes post-administration 5
• Alternative concentrations include 3% for continuous infusion or 23.4% for more concentrated bolus therapy in refractory cases 1, 6
• The 3% solution may provide longer duration of action compared to higher concentrations or mannitol, with sustained ICP control at 120 minutes 3
• Repeated boluses can be administered when ICP remains elevated, typically required every 163 minutes when effects are transient 5

Monitoring Requirements

Measure serum sodium within 6 hours of each bolus and do not re-administer until sodium is <155 mmol/L. 1, 2

• Target serum sodium concentration of 145-155 mmol/L to balance efficacy with safety 2
• Monitor for hypernatremia and hyperchloremia, particularly with continuous infusions 2
• The majority of patients maintain peak sodium levels <155 mmol/L after bolus therapy when properly monitored 2
• Avoid sodium levels exceeding 155-160 mmol/L to prevent complications including osmotic demyelination syndrome 2
• No cases of osmotic demyelination syndrome have been reported with proper monitoring, even with sustained hypernatremia or 23.4% boluses 2, 6

Comparison with Mannitol

Hypertonic saline should be used instead of mannitol, not in combination, and may be preferred in hypovolemic patients. 2

• Three of nine randomized controlled trials in traumatic brain injury showed significant benefit of hypertonic saline over mannitol 1
• Equiosmolar doses (approximately 250 mOsm) produce comparable efficacy between agents 2
• Hypertonic saline may be superior in patients with concurrent hypovolemia, as it provides volume expansion unlike mannitol 2
• In experimental ICH, 3% hypertonic saline maintained significantly higher cerebral perfusion pressure (108.4 vs 79.6 mmHg) and lower water content in lesioned white matter compared to mannitol at 2 hours 3

Critical Limitations on Outcomes

Despite proven ICP reduction, hypertonic saline does not improve neurological outcomes (Grade B evidence) or survival (Grade A evidence) in patients with raised intracranial pressure. 1, 2

• Multiple meta-analyses including 1,283 critically ill patients found no mortality benefit with hypertonic saline 1
• Insufficient evidence from randomized controlled trials confirms improved neurological outcomes in adults with acute ICH 2
• This disconnect between physiologic effect (ICP reduction) and clinical outcomes (survival, neurologic function) is consistent across all studies reviewed 1

Use in Refractory Intracranial Hypertension

Reserve hypertonic saline for patients with ICP >25 mmHg who have exhausted standard management including mannitol and barbiturates. 5

• In patients refractory to standard ICP management protocols, 7.5% hypertonic saline decreased ICP from 33±9 mmHg to 19±6 mmHg within the first hour 5
• Hypertonic saline remains effective even when mannitol response is exhausted 5, 6
• Case reports document safe administration of up to 17 doses of 23.4% hypertonic saline with good outcomes in refractory cases 6

Important Caveats

• Hypertonic saline is not recommended for volume resuscitation in hemorrhagic shock, despite its effectiveness for ICP control 2
• High osmolar loads (>23.4%) carry increased risks of hypernatremia and potential osmotic blood-brain barrier opening with harmful extravasation into brain tissue 7
• Avoid rapid or excessive sodium correction to prevent osmotic demyelination syndrome 2
• The timing of administration may be critical—animal studies suggest ultra-early administration may be most beneficial, though this remains unproven in humans 1
• Continuous infusions require more intensive monitoring of fluid, sodium, and chloride balances compared to bolus therapy 2