Should we use hypertonic saline in patients with hepatic encephalopathy?

Hypertonic Saline in Hepatic Encephalopathy

Hypertonic saline should be used in hepatic encephalopathy only when there is documented elevated intracranial pressure (ICP) in the setting of acute liver failure, not for routine management of hepatic encephalopathy itself. The primary treatments for hepatic encephalopathy remain lactulose and rifaximin, while hypertonic saline serves as a targeted intervention for the life-threatening complication of intracranial hypertension 1.

Clinical Context: Two Distinct Scenarios

Acute Liver Failure with Elevated ICP

• Hypertonic saline is indicated when patients with acute liver failure develop high-grade hepatic encephalopathy complicated by cerebral edema and elevated ICP 1, 2, 3.
• Target serum sodium levels between 145-155 mmol/L to reduce intracranial pressure 1.
• Administer 7.5% hypertonic saline as 250 mL bolus over 15-20 minutes for acute ICP elevation 1.
• The mechanism involves creating an osmotic gradient across the blood-brain barrier, displacing water from brain tissue with maximum effect at 10-15 minutes lasting 2-4 hours 4.
• Evidence shows 23.4% hypertonic saline decreases brain tissue volume and improves Glasgow Coma Scale scores in severe hepatic encephalopathy with cerebral edema 5.

Chronic Hepatic Encephalopathy

• Hypertonic saline is NOT a treatment for chronic hepatic encephalopathy 1.
• Lactulose remains first-line therapy (GRADE II-1, B, 1) 1.
• Rifaximin is the recommended add-on therapy to lactulose for prevention of recurrence (GRADE I, A, 1) 1.
• The 2014 AASLD/EASL guidelines make no recommendation for hypertonic saline in routine hepatic encephalopathy management 1.

Hyponatremia Management: A Critical Distinction

When hyponatremia complicates hepatic encephalopathy, correction must be gradual—NOT with hypertonic saline boluses:

• Correct sodium no faster than 8-12 mEq/L per 24 hours to avoid osmotic demyelination syndrome 2, 3.
• Use free water restriction and increased dietary sodium as first-line approaches 2.
• While there is correlation between hyponatremia and intracranial pressure in acute liver failure, rapid correction with hypertonic saline carries significant risk 1, 3.
• Target sodium 140-145 mmol/L in acute liver failure patients, avoiding levels above 150 mmol/L which are deleterious 1.

Monitoring Requirements When Using Hypertonic Saline

If hypertonic saline is used for documented elevated ICP in acute liver failure:

• Measure serum sodium within 6 hours of bolus administration 1, 4.
• Do not re-administer until serum sodium is <155 mmol/L 1, 4.
• Monitor for hypernatremia and hyperchloremia complications 4, 6.
• ICP monitoring devices carry 7-20% hemorrhagic complication risk in acute liver failure due to coagulopathy 1, 2.

Evidence Limitations and Caveats

Critical limitation: Despite effectiveness in reducing ICP, there is no evidence that hypertonic saline improves neurological outcomes or survival in patients with hepatic encephalopathy 4, 6.

The albumin confusion: One RCT showed IV albumin (not hypertonic saline) given to patients with overt hepatic encephalopathy on rifaximin had no effect on resolution of encephalopathy but improved post-discharge survival 1. This should not be conflated with hypertonic saline use.

Practical Algorithm

1. Identify the clinical scenario:

   • Acute liver failure with high-grade encephalopathy (Grade 3-4) → Consider ICP monitoring and hypertonic saline if elevated ICP documented 1, 2, 7
   • Chronic/episodic hepatic encephalopathy → Use lactulose ± rifaximin, NOT hypertonic saline 1

2. For acute liver failure with suspected elevated ICP:

   • Stabilize airway and hemodynamics first 2, 7
   • Consider transcranial Doppler as non-invasive ICP assessment 1
   • If ICP elevation confirmed: 7.5% hypertonic saline 250 mL over 15-20 minutes 1, 4
   • Target sodium 145-155 mmol/L 1, 4
   • This is a bridge to liver transplantation, not definitive therapy 2, 7

3. For hyponatremia in any hepatic encephalopathy setting:

   • Gradual correction only: ≤10 mmol/L per 24 hours 1, 2
   • Free water restriction and dietary sodium increase 2
   • Avoid rapid bolus correction 3

Bottom line: Hypertonic saline is a specialized intervention for elevated ICP in acute liver failure, not a general treatment for hepatic encephalopathy. Standard therapy remains lactulose and rifaximin for the encephalopathy itself 1.