What is the role of ammonia levels in managing portosystemic encephalopathy?

Utility of Ammonia Levels in Portosystemic Encephalopathy

Ammonia measurement should be performed in patients with delirium or encephalopathy and liver disease primarily to rule out hepatic encephalopathy, as a normal ammonia level brings the diagnosis of HE into question, but ammonia levels should not guide treatment decisions or be used to monitor therapeutic response. 1

Diagnostic Role of Ammonia

When to measure ammonia:

• Measure plasma ammonia in any patient with liver disease presenting with altered mental status or delirium to help confirm or exclude HE as the cause 1
• A normal ammonia level effectively rules out HE and should prompt investigation for alternative causes of encephalopathy 1, 2
• Arterial ammonia levels >200 μg/dL are strongly associated with cerebral herniation risk in acute liver failure 2

Limitations of ammonia measurement:

• Elevated ammonia levels in 84% of PSE patients correlate with severity of encephalopathy but do not correlate with clinical improvement during treatment 3
• Ammonia levels normalize within 3 days of treatment but without correlation to clinical recovery 3
• HE remains a clinical diagnosis based on mental status assessment using the West Haven criteria, not a biochemical diagnosis 1, 2, 4

Clinical Management Approach

Primary assessment strategy:

• Frequent mental status checks using West Haven criteria (grades 1-4) are more valuable than serial ammonia measurements for monitoring disease progression and treatment response 2
• Use the West Haven criteria when at least temporal disorientation is present (grades ≥2) 1
• Add Glasgow Coma Scale for patients with grades III-IV encephalopathy 1

Treatment initiation:

• Lactulose should be initiated based on clinical diagnosis of HE, not on any specific ammonia threshold 4, 5
• The decision to treat is driven by mental status changes and neuropsychiatric symptoms, regardless of ammonia values 4
• Initial dosing: 25 mL lactulose syrup every 1-2 hours until at least 2 soft/loose bowel movements occur, then titrate to maintain 2-3 soft bowel movements daily 4

Precipitating Factors to Address

Identify and treat these factors (present in ~50% of cases, leading to improvement in ~90%): 1

• Gastrointestinal bleeding
• Infections
• Dehydration from diuretics or digestive losses
• Hyponatraemia (maintain sodium >130 mmol/L, ideally >135 mmol/L) 1
• Dyskalaemia
• Acute kidney injury
• Constipation
• Inappropriate proton pump inhibitor use (increases HE risk through dysbiosis) 1
• Benzodiazepines and opioid analgesics (independently associated with increased HE risk) 1

Treatment Algorithm

First-line therapy:

• Lactulose is the first choice for episodic overt HE (GRADE II-1, B, 1) 1
• Titrate to 2-3 soft bowel movements per day 1, 4

Secondary prophylaxis:

• After first episode: Continue lactulose maintenance 1
• After >1 additional episode within 6 months: Add rifaximin 550 mg twice daily to lactulose (GRADE I, A, 1) 1

Alternative/adjunctive therapies for refractory cases:

• IV L-ornithine-L-aspartate (LOLA) 30 g/day can be used as alternative or additional agent (GRADE I, B, 2) 1, 4
• Oral branched-chain amino acids (0.25 g/kg/day) as alternative or additional therapy (GRADE I, B, 2) 1, 4

Critical Care Considerations

For severe encephalopathy (grades III-IV):

• Treat in ICU setting due to aspiration risk 1
• Airway protection through intubation is advisable 2
• Elevate head of bed to 30 degrees 2
• Minimize or avoid sedation to allow neurological assessment 2
• If sedation necessary, propofol is often preferred 2
• Obtain head CT to exclude intracranial hemorrhage or other structural causes 2

Common Pitfalls

Avoid these errors:

• Do not use ammonia levels to guide treatment intensity or monitor therapeutic response 2, 3
• Do not withhold lactulose waiting for ammonia results if clinical diagnosis of HE is apparent 4
• Avoid overuse of lactulose, which can cause aspiration, dehydration, hypernatremia, severe perianal irritation, and paradoxically precipitate HE 4
• Do not restrict protein intake except perhaps for very short periods in severe overt HE with GI bleeding 1
• Systematically re-evaluate PPI prescriptions and discontinue if no formal indication 1