Hepatic Encephalopathy

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This condition 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

  • Viral hepatitis
  • Alcoholic hepatitis
  • Cirrhosis of the liver
  • Hepatocellular carcinoma
  • Drugs e.g. halothane, isoniazid, paracetamol overdose, herbal preparations
  • Fatty liver of pregnancy
  • Precipitating factors in a patient with pre-existing liver disease:
    • Fever
    • Hypotension
    • Infection
    • Fluid and electrolyte imbalance (excessive use of loop diuretics)
    • Sedatives
    • Increased gastrointestinal tract (GIT) protein load e.g. heavy GIT bleeding, alcoholic binge

Symptoms

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

Signs

  • Cyanosis
  • Fetor hepaticus
  • Signs of chronic liver disease
  • 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
    • 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, inarticulate 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)

TreatmentTreatment Objectives

  • To identify and correct precipitating factors promptly
  • To treat underlying cause of liver disease

Non-pharmacological treatment

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

Pharmacological treatment

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) One 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)

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

>2 kg; 15 mg/kg 12 hourly

1-2 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

Hepatic encephalopathy associated with active bleeding (INR > 1.5 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)

Antibiotic prophylaxis in Hepatic encephalopathy (associated with cirrhosis and upper gastro-intestinal haemorrhage)

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

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 with hepatic encephalopathy must be referred to a specialist.