Management of Hepatic Encephalopathy

Primary Treatment Options

The American Association for the Study of Liver Diseases recommends intravenous albumin at 1.5 g/kg/day until clinical improvement or for a maximum of 10 days as the primary fluid for hydration in patients with hepatic encephalopathy 1, 2
Intravenous L-ornithine-L-aspartate (LOLA) at 30 g/day can be administered as an adjunctive therapy to improve recovery time and reduce the grade of hepatic encephalopathy 1, 2
First-line treatment for hepatic encephalopathy is oral lactulose (20-30 g) administered 3-4 times daily, titrated to achieve 2-3 soft bowel movements per day, as recommended by the European Association for the Study of the Liver 1, 3
For patients unable to take oral medications, lactulose can be administered via nasogastric tube 1, 4
For severe hepatic encephalopathy (West-Haven grade 3 or more), an enema with 300 mL lactulose and 700 mL water can be administered 3-4 times daily 1, 4
Rifaximin 400 mg three times daily or 550 mg twice daily can be added as an adjunctive therapy 1, 2

Identifying and managing precipitating factors such as gastrointestinal bleeding, infection, dehydration, or constipation is crucial in the management of hepatic encephalopathy 5
For dehydration, stopping or reducing diuretics and providing fluid therapy with intravenous albumin infusion is recommended 5
Branched-chain amino acids (BCAAs) at 0.25 g/kg/day may be beneficial as an ancillary option in the treatment of hepatic encephalopathy 2
Polyethylene glycol can be used as a substitute for non-absorbable disaccharides in some cases 1

Neomycin and metronidazole should be avoided due to significant side effects including nephrotoxicity, ototoxicity, and peripheral neuropathy 2
Excessive use of lactulose can lead to complications including dehydration, hypernatremia, and severe perianal skin irritation 3, 4
When administering lactulose as an enema, the solution should be retained in the intestine for at least 30 minutes for optimal effect 3
Monitoring for common side effects of lactulose therapy, including bloating and flatulence, is essential 3
For patients with severe encephalopathy, intubation for airway protection should be considered when progressing to grade III or IV encephalopathy 6

The American Association for the Study of Liver Diseases recommends that diuretics be discontinued in patients with overt hepatic encephalopathy, as they can worsen the condition 7, 8, 9
Diuretics can precipitate or worsen hepatic encephalopathy through several mechanisms, including electrolyte disturbances, such as hyponatremia, which is synergistic with hyperammonemia in causing cerebral edema and worsening encephalopathy 10, 11
The European Association for the Study of the Liver suggests that hyponatremia below 130 mmol/L is an independent risk factor for hepatic encephalopathy and is associated with non-response to lactulose treatment 10, 11
Hypokalemia, which can be caused by loop diuretics, independently contributes to encephalopathy, with severe hypokalemia (<3 mmol/L) being a particular concern 7, 8, 9
The International Ascites Club recommends that diuretics be used cautiously, if at all, in patients with ascites and hepatic encephalopathy, due to the risk of worsening encephalopathy and renal impairment 7, 8, 9

The American College of Gastroenterology advises that diuretics should only be reintroduced after complete resolution of hepatic encephalopathy, and then with careful monitoring and at the minimum effective dose 7, 8, 9
Target weight loss should not exceed 0.5 kg/day in patients without edema and 1 kg/day in patients with edema, to avoid excessive diuresis and potential worsening of encephalopathy 7, 8, 9

Large-volume paracentesis (LVP) with albumin is considered safer than diuretics in patients with grade 3 ascites, as it has a lower frequency of hepatic encephalopathy, renal impairment, and hyponatremia compared to diuretic therapy 7, 8, 9
Administering albumin (8 g per liter of ascites removed) can help prevent post-paracentesis circulatory dysfunction 7

Loop diuretics can increase renal ammonia production by inducing metabolic alkalosis and potassium depletion, which contributes to cerebral toxicity in cirrhotic patients. 12
Rapid extracellular fluid volume reduction with loop diuretics destabilizes hemodynamics in cirrhosis and predisposes to encephalopathy. 12

Up to 25 % of hospitalized cirrhotic patients receiving diuretics develop hepatic encephalopathy. 13
Diuretic‑related complications (including encephalopathy) occur in 19–33 % of individuals who start diuretic therapy, and roughly 50 % of these patients require dose reduction or discontinuation. 13

The first‑line action when hepatic encephalopathy appears in a cirrhotic patient on diuretics is to stop all diuretic agents immediately. 14

After full resolution of encephalopathy and normalization of serum sodium (≥ 135 mmol/L), diuretics may be re‑started cautiously.
Re‑introduction should begin with a low‑dose loop diuretic (e.g., furosemide 20–40 mg daily) because loop agents carry a lower hyponatremia risk than thiazides.
Daily weight loss targets must not exceed 0.5 kg in patients without peripheral edema or 1 kg in those with edema to avoid recurrence. [12][13]
Electrolytes should be monitored weekly during the first month after diuretic re‑initiation. 12

Diuretics must be permanently stopped if they repeatedly trigger hepatic encephalopathy, cause renal dysfunction, or produce severe electrolyte disturbances. 14

Serum sodium < 130 mmol/L is an independent risk factor for hepatic encephalopathy and predicts poor response to lactulose.
Diuretics should be temporarily discontinued when sodium falls below 120–125 mmol/L, even in the absence of overt encephalopathy. [12][13]
Loop diuretics induce hyponatremia in 8–30 % of cirrhotic patients, a lower incidence than that seen with thiazide diuretics. 13