How to titrate hypertonic saline (hypertonic sodium chloride solution) in patients with intracerebral hemorrhage (ICH)?

Hypertonic Saline Titration in Intracerebral Hemorrhage

For ICH patients with elevated intracranial pressure, administer 3% hypertonic saline as a continuous infusion targeting serum sodium of 145-155 mmol/L, or use 7.5% hypertonic saline boluses (250 mL over 15-20 minutes) for acute ICP crises, with serum sodium monitoring within 6 hours and avoidance of levels exceeding 155 mmol/L. 1

Bolus Dosing Strategy

For acute ICP elevation or signs of herniation:

• Administer 7.5% hypertonic saline at 250 mL per bolus over 15-20 minutes 1
• Alternative dosing: 2 mL/kg of 7.5% solution has demonstrated significant reduction in both number and duration of intracranial hypertension episodes 1, 2
• Maximum ICP reduction occurs at 10-15 minutes post-infusion, with effects lasting 2-4 hours 1
• Re-bolus may be administered if ICP remains elevated, but only after confirming serum sodium is <155 mmol/L 1
• Typical re-dosing interval is approximately 163 minutes when ICP-lowering effect is transient 2

Continuous Infusion Strategy

For sustained ICP management in ICH:

• Use 3% hypertonic saline as continuous infusion 1, 3
• Target serum sodium concentration: 145-155 mmol/L 1
• Target osmolality: 310-320 mOsmol/kg 3
• Initiate early (within 72 hours of hemorrhage onset) for optimal perihematomal edema control 3
• This approach has shown significant reduction in absolute edema volume between days 8-14 and relative edema volume between days 2-14 compared to controls 3

Monitoring Requirements

Essential parameters to track:

• Measure serum sodium within 6 hours of any bolus administration 1
• Do not exceed serum sodium of 155 mmol/L to prevent complications 1
• Monitor fluid, sodium, and chloride balances to prevent hypernatremia and hyperchloremia 1
• Continuous ICP monitoring is recommended when using hypertonic saline for ICH 1
• Maintain cerebral perfusion pressure >70 mm Hg 4

Comparative Efficacy

Hypertonic saline versus mannitol:

• At equiosmolar doses (approximately 250 mOsm), hypertonic saline demonstrates comparable or superior ICP reduction 1, 5
• 3% NaCl produces significantly higher cerebral perfusion pressure and lower water content in lesioned white matter compared to mannitol in ICH models 5
• Hypertonic saline may have longer duration of action, particularly the 3% solution, with sustained ICP reduction at 120 minutes post-administration 5
• Hypertonic saline is preferred in patients with hypovolemia 1
• Use hypertonic saline instead of, not in conjunction with mannitol 1

Graded Approach to ICP Management

Begin with simple measures before escalating:

• Elevate head of bed 4
• Provide analgesia and sedation 4
• Progress to osmotic therapy (hypertonic saline) when simple measures fail 4
• More aggressive therapies include CSF drainage via ventricular catheter, neuromuscular blockade, and hyperventilation 4

Critical Safety Considerations

Important caveats:

• Despite effectiveness in reducing ICP, there is no evidence that hypertonic saline improves neurological outcomes (Grade B) or survival (Grade A) in ICH patients 1
• Avoid rapid or excessive sodium correction to prevent osmotic demyelination syndrome 1
• No cases of osmotic demyelination syndrome have been reported with proper monitoring, even with bolus doses of 23.4% hypertonic saline 1
• Hypertonic saline is not recommended for volume resuscitation in hemorrhagic shock 1
• Monitor for cardiac arrhythmias, though these occur at similar rates as with other osmotic agents 3

Evidence Quality

The evidence base for hypertonic saline in ICH is limited, with the European Stroke Organisation noting insufficient RCT evidence to make strong recommendations on ICP-lowering measures 4. One nonrandomized feasibility study showed 3% hypertonic saline led to less perihematomal edema and a mortality trend favoring treatment 4. The strongest evidence comes from a 2011 study demonstrating that early continuous 3% hypertonic saline infusion (targeting sodium 145-155 mmol/L) reduced perihematomal edema evolution and ICP crises, with a trend toward reduced mortality (11.5% vs 25%, p=0.078) 3.