Fulminant Hepatic Failure


Fulminant Hepatic Failure = rapid onset of encephalopathy in conjunction with hepatic synthetic failure.


  • Drugs – paracetamol, idiosyncratic, illicit, herbal/alternative (amanita mushroom), halothane
  • Alcohol
  • Viruses – HAV, HBV +/-D, HCV, HEV, CMV, EBV, HSV
  • Extras – acute fatty liver of pregnancy, HELLP, toxins, ischaemic necrosis, vascular, metabolic, autoimmune, Wilson’s disease, Budd-Chiari, post hepatic surgery, idiopathic
  • Sepsis


  • sleep disturbance
  • asterixis
  • hyperreflexic
  • can be hemiplegic

Precipitating factors:

  • GIH
  • infection
  • hypokalaemia
  • sedatives
  • increased protein intake
  • progressive hepatic dysfunction
  • renal failure


  • A = acute liver failure
  • B = presence of portocaval shunting
  • C = in context of cirrhosis

Grade I -> IV

  • mildly drowsible but rousable and coherent
    -> responding to pain/unconscious


  • elevated ammonia (not required to make diagnosis of encephalopathy)
  • urine and serum toxicology screen
  • hepatitis serology
  • ceruloplasmin
  • antinuclear antibodies
  • smooth-muscle antibodies
  • serum protein electrophoresis
  • CMV and EBV serology
  • serum phosphate: decrease suggestive of hepatocyte recovery and regeneration -> good prognostic marker



A – intubated if unresponsive from encephalopathy (RSI to prevent aspiration)
B – often have respiratory failure from pleural effusions and may have aspirated requiring mechanical ventilation
C – fluid maintenance, often have a hyperdynamic circulation, vasoactive medication
D – monitoring for intra-cranial hypertension: ICP bolt, mannitol, propofol, thiopentone, moderate hypothermia (32-33 C), hypertonic saline

  • Once stabilized early consultation with Liver Transplant Centre
  • Vigilant monitoring for infection (bacterial, fungal)

Specific treatment

  • paracetamol OD: N-acetylcysteine 150mg/kg LD, 50mg/kg over 4 hours, 100mg/kg over 16 hours
  • Amanita poisoning: penicillin
  • acute fatty liver of pregnancy: delivery of infant and placenta
  • Wilson’s disease: zinc and trientine therapy, apheresis
  • Acute Budd-Chiari: TIPS, surgical decompression, thrombolysis -> transplantation
  • HSV: acyclovir
  • ischaemic: restore circulation to liver
  • encephalopathy:
    — lactulose -> increases ammonia elimination
    — metronidazole -> alter gut flora to decrease ammonia production
    — flumazenil (controversial)
  • coagulopathy:
    only treat with FFP if bleeding or prior to procedures
    — FVIIa safe and effective
    — continue until encephalopathy resolves
  • TIPS procedure (see TIPS)
  • short-term extracorporeal hepatic support (see MARS)

Criteria for Transplantation (King’s College Criteria)

Paracetamol induced fulminant hepatic failure

  • pH < 7.3 or INR > 6.5 (PT > 100s)
  • Cr > 300micromol/L
  • grade III or IV encephalopathy

Non-paracetamol induced fulminant hepatic failure

  • INR > 6.5 (PT > 100s) or any 3 of the following variables:

(1) age < 10 or > 40 yrs
(2) aetiology – non A, non B hepatitis, halothane hepatitis, idiosyncratic drug reactions
(3) duration of jaundice before encephalopathy > 7 days
(4) INR > 3.5 (PT > 50s)
(5) bilirubin > 300micromol/L

General treatment

  • electrolyte balance (hypokalaemia, hyponatraemia, hypophosphataemia)
  • Na+ restriction + diuretics -> decreases ascites
  • frequent glucose monitoring (hypoglycaemia)
  • nutrition (amino acids, lipids, glucose, essential elements)
  • renal failure is common (especially in paracetamol OD -> direct renal toxic effects)
  • feed


  • management in ICU
  • early discussion with liver transplant unit (prior to reversal of coagulopathy)
  • discussion with family (high mortality)


  • cerebral oedema and herniation
  • coagulopathy
  • GI bleed
  • sepsis
  • renal failure
  • hypoglycaemia
  • electrolyte abnormalities
  • respiratory failure: impaired ventilation c/o coma, pleural effusions, ARDS, intra-pulmonary shunts, aspiration, sepsis


  • targeted CPP management with insertion of an ICP monitor
  • MARS therapy
  • use of FVIIa

References and Links

Journal articles

  • Craig DG, Lee A, Hayes PC, Simpson KJ. Review article: the current management of acute liver failure. Aliment Pharmacol Ther. 2010 Feb 1;31(3):345-58. PMID: 19845566.
  • Laleman W, Verbeke L, Meersseman P, Wauters J, van Pelt J, Cassiman D, Wilmer A, Verslype C, Nevens F. Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):523-37; quiz 537.PMID: 21780899.
  • Lee WM. Recent developments in acute liver failure. Best Pract Res Clin Gastroenterol. 2012 Feb;26(1):3-16. PMC3551290.
  • Patton H, Misel M, Gish RG. Acute liver failure in adults: an evidence-based management protocol for clinicians. Gastroenterol Hepatol (N Y). 2012 Mar;8(3):161-212. PMC3365519.
  • Saliba F, Samuel D. Acute liver failure: Current trends. J Hepatol. 2013 Apr 6. PMID: 23567082.

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.