How should a patient with hepatic encephalopathy on lactulose (lactulose) 30mls three times a day (tds), Rifaximin (Rifaximin) 550mg twice a day (bd), thiamine (thiamine) 100mg twice a day (bd), Spironolactone (spironolactone) 75mg once a day (od), Furosemide (furosemide) 80mg in the morning and 40mg at lunchtime, be assessed and managed given persistent confusion and disorientation?

Management of Persistent Hepatic Encephalopathy

The first step in managing this patient with persistent hepatic encephalopathy despite current therapy is to identify and address potential precipitating factors, followed by optimization of the current medication regimen. 1

Assessment Algorithm

1. Identify Precipitating Factors

• Gastrointestinal bleeding: Check for melena, hematemesis, perform rectal examination
• Infection: Complete blood count, cultures (blood, urine, ascitic fluid if present)
• Constipation: Abdominal examination, assess stool frequency
• Electrolyte imbalances: Check sodium, potassium, calcium levels
• Dehydration: Assess skin turgor, blood pressure, review diuretic dosing
• Renal dysfunction: Check creatinine, BUN
• Medication compliance: Verify proper administration of lactulose and rifaximin
• Medication side effects: Check for over-sedation from other medications
• Acute hepatic injury: Liver function tests

2. Medication Optimization

Current regimen assessment:

• Lactulose 30ml TDS: May be inadequate dosing
• Rifaximin 550mg BD: Appropriate dosing
• Diuretics: Spironolactone 75mg OD, Furosemide 80mg morning and 40mg lunchtime

Management Recommendations

1. Optimize lactulose dosing:

   • Titrate lactulose to achieve 2-3 soft bowel movements daily 1
   • Consider increasing to 30-45ml QID if needed
   • If oral intake is inappropriate due to severe HE, administer lactulose enema (300ml lactulose in 700ml water) 1

2. Ensure proper rifaximin administration:

   • Continue rifaximin 550mg twice daily 2
   • Verify patient is taking medication correctly

3. Review diuretic therapy:

   • Consider temporarily reducing diuretic doses if dehydration is suspected
   • Monitor electrolytes closely, especially sodium and potassium

4. Additional therapeutic options:

   • Consider adding oral branched-chain amino acids (BCAA) 1
   • Consider intravenous L-ornithine L-aspartate (LOLA) or albumin 1
   • In severe cases unresponsive to medical therapy, consider polyethylene glycol if ileus is present 1

5. Nutritional management:

   • Ensure adequate protein intake (1.2-1.5 g/kg/day) 1
   • Recommend small, frequent meals (4-6 times daily including night snack) 1
   • Daily energy intake should be 35-40 kcal/kg 1
   • Avoid protein restriction as it can worsen sarcopenia 1, 3

6. Consider liver transplantation evaluation:

   • Persistent HE despite optimal medical therapy is an indication for liver transplantation 1

Monitoring Response

1. Daily assessment of mental status using West Haven criteria 3
2. Monitor serum ammonia levels, though not for diagnosis but to track treatment response
3. Evaluate for medication side effects, particularly diarrhea from lactulose
4. Monitor renal function and electrolytes regularly, especially with diuretic therapy

Important Caveats

• Avoid benzodiazepines as they can worsen HE; if sedation is required, use medications with short half-lives like propofol or dexmedetomidine 1
• Routine brain imaging is not recommended unless this is the first episode of confusion, there are focal neurological signs, or there is inadequate response to therapy 1
• Patient and caregiver education is crucial to improve adherence and reduce readmissions 1
• Rifaximin combined with lactulose has shown better outcomes than lactulose alone in treatment-resistant HE 4, 5, though some studies show no significant difference 6

If the patient fails to improve despite optimized therapy and addressing precipitating factors, consider referral for liver transplantation evaluation, as the survival rate after an episode of overt HE is only 42% at 1 year and 23% at 3 years 1.