What is the role of hypertonic saline (HS) in managing raised Intracranial Pressure (ICP)?

Hypertonic Saline in Raised Intracranial Pressure

Hypertonic saline is effective at reducing elevated intracranial pressure (Grade A evidence) and should be used in the treatment algorithm for raised ICP, preferably instead of mannitol, though it does not improve neurological outcomes or survival. 1

Mechanism and Efficacy

Hypertonic saline creates an osmotic pressure gradient across the blood-brain barrier by transiently increasing extracellular osmolarity, displacing water from brain tissue to the hypertonic environment and reducing cerebral edema. 2 The maximum effect occurs after 10-15 minutes and lasts 2-4 hours. 2

The evidence base is robust for ICP reduction but limited for patient-centered outcomes:

• Multiple randomized controlled trials in traumatic brain injury patients demonstrate significant ICP reduction, with three of four studies comparing hypertonic saline to mannitol showing benefit with hypertonic saline 1
• Case-control studies confirm ICP reduction in traumatic brain injury, subarachnoid hemorrhage, stroke, acute liver failure, and tumor surgery 1
• Despite effectiveness in reducing ICP (Grade A), there is no evidence of improved neurological outcomes (Grade B) or survival benefit (Grade A) 1, 2

Dosing Recommendations

For bolus therapy (most common approach):

• Administer 7.5% hypertonic saline at 250 mL per bolus over 15-20 minutes for acute ICP elevation or signs of brain herniation 2
• This concentration and volume showed superior efficacy compared to equivalent volumes of 20% mannitol in multiple studies 1, 2
• Re-administration may be considered if ICP remains elevated, typically after 163 ± 54 minutes when the effect becomes transient 3

For continuous infusion therapy:

• Use 3% hypertonic saline as continuous infusion targeting serum sodium of 145-155 mmol/L 2
• This approach is particularly validated in pediatric traumatic brain injury, acute liver failure, and stroke patients 1, 2
• Mean treatment duration in pediatric studies was 7.6 days without adverse effects 1

Critical Monitoring Parameters

Serum sodium must be measured within 6 hours of bolus administration and should not exceed 155 mmol/L before re-dosing. 1, 2 The majority of patients have peak sodium levels <155 mmol/L after bolus therapy. 1

Target serum sodium concentration: 145-155 mmol/L for both bolus and continuous infusion strategies. 2 Avoid exceeding 155-160 mmol/L to prevent complications. 2

Monitor fluid, sodium, and chloride balances to prevent hypernatremia and hyperchloremia, especially with continuous infusions. 2

Comparison with Mannitol

Hypertonic saline should be used instead of and not in conjunction with mannitol. 1, 2 The evidence supporting this recommendation includes:

• 7.2% hypertonic saline with hydroxyethyl starch caused greater ICP decrease than 15% mannitol (57% vs 48%, p<0.01) with lower effective dose (1.4 ml/kg vs 1.8 ml/kg) 4
• Hypertonic saline may be preferred in patients with hypovolemia, as mannitol can cause dehydration over time while hypertonic saline helps maintain normovolemia and cerebral perfusion 5
• In pediatric populations, hypertonic saline produced greater ICP reduction, shorter mechanical ventilation duration, shorter PICU stay, and lower mortality compared to mannitol 2

Safety Profile

No evidence of osmotic demyelination syndrome has been reported with proper monitoring, even with bolus doses of 23.4% hypertonic saline or sustained hypernatremia. 1, 2 Post-herniation MRI studies in 68 patients receiving 23.4% hypertonic saline failed to detect osmotic demyelination. 1

The highest recorded sodium level in a survivor was 169 mmol/L, with most levels returning to normal by 4-24 hours. 1 In pediatric studies, mean highest serum sodium was 170.7 mmol/L without adverse effects. 1

Critical safety warning: Inadvertent direct injection or absorption of concentrated sodium chloride (particularly 23.4%) may cause sudden hypernatremia leading to cardiovascular shock, central nervous system disorders, extensive hemolysis, and cortical necrosis of the kidneys. 6 The solution must be diluted prior to administration per FDA labeling. 6

Clinical Populations

Effective in multiple etiologies of raised ICP:

• Traumatic brain injury (most studied population) 1
• Subarachnoid hemorrhage 1
• Acute liver failure (30% hypertonic saline infusion) 1
• Stroke 1
• Pediatric traumatic brain injury (3% continuous infusion) 1, 2

Important Caveats

Hypertonic saline is not recommended for volume resuscitation in hemorrhagic shock. 2 However, in combined hemorrhagic shock with severe head trauma and focal neurological signs, a bolus may be considered due to its osmotic effect. 2

Avoid rapid or excessive sodium correction to prevent osmotic demyelination syndrome, though this has not been reported with proper monitoring protocols. 1, 2

The evidence base consists primarily of small, heterogeneous studies with high risk of bias, particularly the case-control studies. 1 Meta-analyses have shown no mortality benefit (relative risk 0.88,95% CI 0.74-1.05). 1