Hepatic Encephalopathy

Introduction

Hepatic encephalopathy is a complication of either acute or chronic liver disease.
It presents with disordered central nervous system function, due to inability of the liver to detoxify ammonia and other chemicals.

Causes of hepatic encephalopathy

The following are the causes of hepatic encephalopathy:

  1. Viral hepatitis
  2. Alcoholic hepatitis
  3. Cirrhosis of the liver
  4. Hepatocellular carcinoma
  5. Drugs e.g. halothane, isoniazid, paracetamol overdose, herbal preparations
  6. Fatty liver of pregnancy

Precipitating factors in a patient with pre-existing liver disease:

  1. Fever
  2. Hypotension
  3. Infection
  4. Fluid and electrolyte imbalance (excessive use of loop diuretics)
  5. Sedatives
  6. Increased gastrointestinal tract (GIT) protein load e.g. heavy GIT bleeding, alcoholic binge

Symptoms of hepatic encephalopathy

  1. Jaundice
  2. Confusion
  3. Disturbed consciousness which progresses as follows:
    • disorder of sleep, hypersomnia and inversion of sleep rhythm, apathy and eventually coma
  4. Personality changes

Signs of hepatic encephalopathy

  1. Cyanosis
  2. Fetor hepaticus
  3. Signs of chronic liver disease
  4. Neurological abnormalities:
    • Speech impairment
    • Asterixis (a flapping tremor) indicates pre-coma and strongly supports the diagnosis of encephalopathy
    • Inability to draw or construct objects e.g. a 5-pointed star
    • Incoordination
    • Lethargy
  5. Encephalopathy
    • Grade 1: Mild confusion, irritable, tremor, restless
    • Grade 2: Lethargic responses, decreased inhibitions, dis orientation, agitation, asterixis
    • Grade 3: Stuporous but arousable, aggressive bursts, inar ticulate speech and marked confusion
    • Grade 4: Coma

Investigations

  • FBC
  • Blood glucose
  • Liver function tests
  • Blood urea and electrolytes
  • Hepatitis B-surface-Antigen.
  • Hepatitis C screen
  • Prothrombin time, INR
  • Infection screen (blood culture, urine RE, chest X-Ray, diagnostic ascitic tap)

Treatment for hepatic encephalopathy

Objectives

  1. To identify and correct precipitating factors promptly
  2. To treat underlying cause of liver disease

Non-pharmacological treatment

  1. Place in the coma position if unconscious
  2. Maintain fluid and electrolyte balance (avoid dehydration and electrolyte abnormalities such as hypokalaemia)
  3. Monitor temperature, pulse and respiratory rate, blood pressure, pupils, urine output and blood glucose regularly
  4. Avoid alcohol, paracetamol and other hepatotoxic agents
  5. Avoid sedatives such as benzodiazepines and drugs that impair the coagulation system
  6. Patients should NOT have their protein intake restricted
    • Maintain an adequate protein intake of 1.2-1.5 g/kg per day
  7. Encourage intake of high carbohydrate diet by mouth or NG tube

Pharmacological treatment

A. Measures to correct hydration status and nutrition

Evidence Rating: [A]
Adults
Dextrose saline (5-10% dextrose in 0.9% saline) , IV, 500 ml 8 hourly (according to requirements)

And

High potency Vitamin B, IV, (formulated as two separate vials) pair of vials daily (added to glucose IV solution)
Children
Dextrose saline (4.3% in 0.18% saline), IV,

And

High potency Vitamin B, IV, (formulated as two separate vials)

B. Measures to lower blood ammonia concentration

1st Line Treatment
Evidence Rating: [A]
Lactulose, oral,
Adults
Start with 30-45 ml (20-30 g), 6-12 hourly
(Review dose to maintain 2-3 semi-solid stools per day)
Children and Adolescents
Start with 5-20 ml 6-12 hourly
(Review dose to maintain 2-3 semi-solid stools per day)
Neonates
Start with 0.5-5 ml 6-12 hourly
(Review dose to maintain 2-3 semi-solid stools per day)

Or

Lactulose, rectal
300 ml diluted in 700 ml water (via rectal balloon catheter) 4-6 hourly, retain in the rectum for 30-60 minutes.
(Review dose to maintain 2-3 semi-solid stools per day)

And

Metronidazole, oral,
Adults; 400 mg 8 hourly
Children: 15 mg/kg 12 hourly
Neonates

  • 1-2 kg: 15 mg/kg 12 hourly
  • > 2 kg; 7.5 mg/kg 12 hourly

2nd Line Treatment
Evidence Rating: [A]
Rifaximin, oral,
Adults: 550 mg 12 hourly
Children

  • > 12 years; 200 mg 8 hourly
  • < 12 years; Not recommended

C. Hepatic encephalopathy associated with active bleeding (INR or platelet count < 50 x 109/L)

Adults and Children (liaise with Haematology)
Fresh frozen plasma, IV, (for INR > 1.5

Or

Platelet concentrate, IV, (platelet count < 50 x 10⁹/L)

D. Hepatic encephalopathy (associated with cirrhosis and upper gastro-intestinal haemorrhage)

Antibiotic prophylaxis
Patients in whom oral administration is not possible,
Evidence Rating: [A]
Ciprofloxacin, IV,
Adults: 400 mg 8-12 hourly (administered over 60 minutes)

Or

Ceftriaxone, IV, 1 g daily for 7 days

Or

Ciprofloxacin, oral, 500 mg 12 hourly

Or

Norfloxacin, oral, 400 mg 12 hourly for 7 days

E. Hepatic encephalopathy precipitated by bacterial infection

Note

A diagnosis of SBP is established if the neutrophil count in the ascitic fluid is > 250 cells/mL, culture results positive and surgically treatable causes are excluded.
Patients with suspected SBP should be started on empiric antibiotics immediately after ascitic fluid is obtained pending results:

 
Evidence Rating: [A]
1st Line treatment
Ciprofloxacin, IV, 400 mg 8-12 hourly for 2 days (to be administered over 60 minutes)

Then

Ciprofloxacin, oral, 500 mg 12 hourly for 5 days
Note

Avoid in patients with prior fluoroquinolone therapy as SBP prophylaxis or history of resistance.

2nd Line treatment
Cefotaxime, IV, 2 g 8 hourly for 7 days

Or

Ceftriaxone, IV, 2 g daily for 7 days

Referral Criteria

Refer patients if the condition does not improve.
All children hepatic encephalopathy must be referred to a specialist.