What is the best treatment approach for a patient with liver cirrhosis, hyperammonemia, and agitation in a skilled nursing facility (SNF)?

Treatment of Cirrhosis with Hyperammonemia and Agitation in SNF

Start empiric lactulose immediately at 25 mL every 1-2 hours until achieving 2-3 soft bowel movements daily, then titrate to maintain this frequency, while simultaneously investigating and treating precipitating factors such as infection, GI bleeding, constipation, and electrolyte disorders. 1

Immediate Empiric Management

Lactulose Therapy

• Initiate lactulose without waiting for diagnostic workup or ammonia confirmation 1
• Administer 25 mL orally or via nasogastric tube every 1-2 hours until bowel movements occur 2
• Target 2-3 soft bowel movements per day as the therapeutic endpoint 1, 3
• If ileus is present or suspected, hold oral lactulose and use rectal route: 300 mL lactulose in 700 mL water (total 1 L) as enema 1
• Monitor electrolytes closely to prevent dehydration and hypernatremia from excessive lactulose 1

Rifaximin Consideration

• Add rifaximin 550 mg twice daily as adjunctive therapy to lactulose 1, 4
• The FDA label indicates rifaximin is approved for reduction in risk of overt HE recurrence in adults, with 91% of trial patients using concomitant lactulose 4
• While the role of rifaximin in acute/critically ill settings warrants further investigation, it is established for secondary prevention 1

Identify and Treat Precipitating Factors

Infection Screening and Treatment

• Start empirical broad-spectrum antibiotics if infection is suspected or patient is high-risk 1
• Common precipitants include infections, which are reasonable to treat empirically in high-risk patients 1
• Obtain cultures (blood, urine, ascitic fluid if present) before antibiotics but do not delay treatment 1

Other Precipitants to Address

• GI bleeding: Check for melena, hematemesis; investigate and treat promptly 1
• Constipation: Often overlooked but critical precipitant 1
• Electrolyte disorders: Check and correct hypokalemia, hyponatremia, alkalosis 1
• Acute kidney injury: Assess renal function and treat appropriately 1
• Medications: Review for CNS depressants, sedatives, or inappropriate lactulose dosing (under or overuse) 1
• Dehydration: Assess volume status and correct 1

Severity Assessment and Transfer Considerations

Grade the Hepatic Encephalopathy

• Use West Haven criteria to characterize severity 1
• Grade 3 or 4 HE requires ICU-level care 1
• If patient has Grade 3-4 HE (stupor, somnolence, or coma), consider transfer from SNF to acute care hospital 1

When to Consider Alternative Diagnoses

• If this is the first episode of altered mental status, investigate non-HE causes 1
• If patient does not respond to adequate empirical HE therapy, workup liver-unrelated causes (alcohol withdrawal, structural brain injury, drug toxicity) 1
• Brain imaging is NOT routinely needed for recurrent, nonfocal presentations similar to prior episodes 1

Ammonia Testing: Not Recommended for Routine Management

AASLD Guidance on Ammonia

• Routine ammonia level testing in cirrhotic patients with altered mental status is NOT recommended 1, 5
• Ammonia levels are variable within patients and laboratories, and may be elevated in non-HE conditions 1
• A low ammonia level can help rule out HE and should prompt investigation of alternative causes 1, 5
• Do not chase ammonia levels; clinical improvement (mental status, asterixis resolution) matters more than absolute values 5, 6

Evidence Against Ammonia-Guided Therapy

• A 2020 study of 1,202 HE admissions found no correlation between ammonia levels and lactulose dosing (R = 0.0026), demonstrating that ammonia levels do not guide therapy in clinical practice 6
• Patients with elevated ammonia received identical lactulose doses (161 mL) as those with normal ammonia levels 6

Nutritional and Supportive Care

Protein Intake

• Do NOT restrict protein long-term as this induces protein catabolism, hepatic dysfunction, and sarcopenia 1
• Target daily protein intake of 1.2-1.5 g/kg and energy intake of 35-40 kcal/kg 1
• Small frequent meals (4-6 times daily including night snack) improve outcomes 1

Education for SNF Staff and Caregivers

• Educate on effects and side effects of lactulose (diarrhea is expected) 1
• Emphasize importance of medication adherence 1
• Train staff to recognize early symptoms of recurring HE 1
• Establish clear action plan if recurrence begins 1

Common Pitfalls to Avoid

• Do not delay lactulose waiting for ammonia results; treat based on clinical presentation 1, 5
• Do not over-titrate lactulose causing severe dehydration, hypernatremia, or aspiration risk 2, 5
• Do not use rifaximin as monotherapy for acute ammonia lowering; it requires concomitant lactulose 2, 4
• Do not routinely image the brain in patients with recurrent, nonfocal presentations 1
• Do not discontinue lactulose abruptly once patient improves; those with prior HE episodes need long-term secondary prophylaxis 1, 5

Alternative Therapy: Polyethylene Glycol

• Polyethylene glycol (PEG) has been studied as an alternative to lactulose with comparable or superior efficacy 1, 7
• A 2017 trial showed PEG plus lactulose improved HESA scores at 24 hours more effectively than lactulose alone (p=0.04) and decreased hospital length of stay (p=0.03) 7
• Consider PEG if patient is at risk of ileus or abdominal distention 1