Management of Hepatic Encephalopathy by Grade
Grade-Specific Management Algorithm
All patients with overt hepatic encephalopathy (grades I-IV) require immediate treatment with a four-pronged approach: stabilization of altered consciousness, exclusion of alternative causes, identification and correction of precipitating factors, and empirical HE treatment with lactulose. 1
Grades I-II (Mild to Moderate)
Setting and Monitoring
- Manage on a medicine ward with frequent mental status checks, though ICU is preferable 1, 2
- Transfer to ICU immediately if level of consciousness declines 2
- Avoid sedatives as they worsen encephalopathy and have delayed clearance in liver failure 2
Clinical Features to Identify
- Grade I: Mild alterations in consciousness, subtle personality changes, decreased attention, sleep disturbances, irritability or apathy, difficulty with complex cognitive tasks 2
- Grade II: Mild disorientation (especially temporal), pronounced lethargy, inappropriate behavior, asterixis, dysarthric or slow speech 2
Precipitating Factor Management
Identifying and correcting precipitating factors resolves HE in nearly 90% of patients and is the cornerstone of management 1, 3
Search systematically for:
- Infections (present in 64% of ICU cases) 4
- Gastrointestinal bleeding (36% of cases) 4
- Acute kidney injury (63% of cases) 4
- Constipation 1
- Dehydration and electrolyte disturbances (hyponatremia in 22%) 1, 4
- Sedative medications (41% of cases) 4
- TIPS placement (12% of cases) 4
First-Line Pharmacologic Treatment
Start lactulose 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements daily 3, 5
- Achieves clinical response in approximately 75% of patients 3, 5
- Reduces blood ammonia levels by 25-50% 5
- Can be administered via nasogastric tube if unable to swallow 1, 3
- Common pitfall: Overuse leads to aspiration, dehydration, hypernatremia, and perianal skin irritation 3
Diagnostic Workup
- Obtain brain CT to exclude other causes of altered mental status (intracranial hemorrhage, stroke), though it has limited utility for identifying cerebral edema 1, 2
- Do not rely on ammonia levels for diagnosis, staging, or prognosis—a normal value should prompt diagnostic reevaluation 1, 2
- Consider animal naming test to detect covert (minimal) hepatic encephalopathy 2
Metabolic Monitoring
- Check glucose, potassium, magnesium, and phosphate levels frequently 1, 2
- Monitor coagulation parameters, complete blood counts, and arterial blood gas 1
Grades III-IV (Severe to Coma)
Critical Care Management
Patients with grade III-IV encephalopathy require ICU admission with intensive monitoring 1
- Intubate the trachea (may require sedation) to protect airway 1
- Elevate head of bed 1
- Minimize stimulation 1
Cerebral Edema Risk
- Cerebral edema occurs in 25-35% of grade III patients and 65-75% of grade IV patients 1
- Consider placement of ICP monitoring device, though this remains controversial due to coagulopathy risk 1
- Treat severe ICP elevation or first clinical signs of herniation with mannitol 1
- Hyperventilation has short-lived effects; reserve for impending herniation 1
Pharmacologic Treatment
Continue lactulose via nasogastric tube at 25 mL every 12 hours, titrated to 2-3 soft stools daily 1, 3, 5
Add rifaximin 550 mg twice daily if:
- Patient has recurrent episodes despite lactulose 3, 6
- This is the second or subsequent episode 3
- Reduces HE recurrence risk by 58% when added to lactulose 3
Alternative Therapies for Refractory Cases
- IV L-ornithine L-aspartate for patients nonresponsive to conventional therapy (oral form is ineffective) 3
- Oral branched-chain amino acids as alternative or additional therapy (IV form ineffective for acute episodes) 3
Infection Surveillance
- Surveillance for and prompt antimicrobial treatment of infection is required 1
- Antibiotic prophylaxis possibly helpful but not proven 1
Seizure Management
Secondary Prophylaxis (All Grades After First Episode)
Secondary prophylaxis with lactulose is mandatory after the first episode of overt HE 1, 2, 3
Prophylaxis Regimen
- Lactulose: Continue indefinitely, titrated to 2-3 soft stools daily 3
- Add rifaximin 550 mg twice daily after the second episode or if recurrence occurs despite lactulose 3, 6
- The combination improves recovery within 10 days and shortens hospital stays 3
When to Discontinue Prophylaxis
Discontinue only when:
- Precipitating factors are well-controlled 2
- Infections are treated 2
- Variceal bleeding is resolved 2
- Liver function or nutritional status significantly improved 2
Nutritional Management (All Grades)
Do not restrict protein—this worsens malnutrition and sarcopenia, which are risk factors for HE 3
Nutritional Strategy
- Provide moderate hyperalimentation with small, frequent meals throughout the day 2, 3
- Include a late-night snack 2, 3
- Avoid fasting periods which worsen HE 3
- Multivitamin supplementation is generally recommended 2
- Address malnutrition present in approximately 75% of patients 2
Liver Transplantation Evaluation
Evaluate for liver transplantation after the first episode of overt HE 2
Recurrent intractable overt HE with liver failure is an indication for liver transplantation 1, 2
Special Consideration
- Evaluate for large spontaneous portosystemic shunts amenable to embolization in patients with preserved liver function and recurrent HE 3
Critical Pitfalls to Avoid
- Failing to systematically search for precipitating factors, which cause 90% of cases 2, 3
- Not titrating lactulose adequately to achieve 2-3 stools per day 2, 3
- Confusing HE with other causes of altered mental status (intracranial hemorrhage, infection, metabolic derangements) 2, 3
- Not initiating secondary prophylaxis after the first episode 2, 3
- Relying exclusively on ammonia levels for diagnosis—they lack diagnostic, staging, or prognostic value 1, 2
- Restricting protein intake, which worsens outcomes 3
- Multiple concomitant precipitating factors (present in 82% of ICU patients) are associated with death or liver transplantation—screen systematically for all factors 4