BCC4: David anderson on Acute Liver Failure


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David Anderson gives an entertaining and informative talk about Acute Liver Failure at BCC4. He covers thinking about diagnosis, management and prognosis of acute liver failure. The podcast for this presentation is found at www.intensivecarenetwork.com

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  • Acute Liver Failure (ALF), also known as fulminant hepatic failure, can be a scary condition to deal with for those who don’t work in specialist liver units. This is a simple guide for emergency physicians and intensivists to the assessment and management of these complex patients with acute liver failure while awaiting transfer to the liver transplant center.
  • A more australian ALF
  • Lets look at a case.
    You are the intensivist in a small regional hospital and are called to see a 30 year old woman with jaundice and confusion
    She is warm and vasodilated, tachycardic and hypotensive,
    She is deeply jaundiced with gingival bleeding, but no stigmata of chronic liver disease
    A VBG which shows a severe metabolic acidosis with a lactate of 8, and a Glucose of 2.5
  • They don’t always present like this of course, and sometimes you have to do quite a bit of detective work
  • There is no single accepted definition of ALF but most societies’ definitions include the development of coagulopathy and/or encephalopathy within a short period after the onset of symptoms or development of jaundice in someone with no previous liver disease. While the latency between onset of jaundice and onset of encephalopathy is typically only a few days, the most commonly used definition (the O’Grady criteria) allow up to 26 weeks.
  • It is important to establish the aetiology, as different aetiologies have different clinical courses and chances of spontaneous regeneration of hepatic tissue. Common aetiologies are;
    Paracetamol poisoning
    Acute viral hepatitis
    Idiosyncratic drug reactions
    Other causes such as death cap mushrooms and wilsons disease
    up to 1/4 of cases have no cause found
  • - Once you have identified a patient with ALF, you should contact the regional liver transplant center for advice and to arrange referral if appropriate
    - Most patients are sick enough to justify medical retrieval
  • While most centers wont be able to run all of these tests, a thorough blood workup is essential, as there are often multiple derangements. At the least you should send;
    full blood count
    full biochemistry
    liver function tests
    coagulation including fibrinogen
    arterial or venous blood gas with lactate
    Blood group and screen
    Paracetamol level
  • Lets look at management now
    N-Acetyl cysteine (NAC) should be administered to all patients where paracetamol poisoning is confirmed or suspected
    Regardless of time interval since paracetamol ingestion
    It should be continued until the patient receives a liver transplant or leaves ICU
    It is very safe
    Consider administering NAC to all patients
    May be beneficial in early grade encephalopathy
  • As with all patients, good general ICU housekeeping is vital
    Be vigilant for, and promptly correct hypoglycaemia
    which is common in ALF,
    an infusion of 50% dextrose may be required to maintain euglycaemia
    All patients should have stress ulcer prophylaxis
    Enteral feeding should be commenced early, unless contra-indicated
    Consider low protein feeds and Consider concentrated feeds if neutral or negative fluid balance is difficult to maintain
  • A vasodilated, high cardiac output state is very common in ALF and almost all patients will require invasive monitoring and vasopressor support
    Place invasive lines early.
    ultrasound guided internal jugular lines should be placed by the most experienced person available.
    If you have a TEG, this should be used to guide correction of coagulopathy
    Consider inserting a dialysis catheter at the time of central line insertion
  • Consider using CO monitoring if available
    Consider aiming for a higher than normal MAP to help ensure adequate cerebral perfusion
    Use fluid boluses initially
    but norad plus or minus vasopressin or terlipressin will likely be required
    Very occasionally an inotrope will be required
    Consider low dose corticosteroids if vasopressor requirements are significant
    Have a high index of suspicion for occult sepsis in addition to vasoplegia if vasopressor requirements are high or rising rapidly
  • Encephalopathy develop very rapidly. Intracranial hypertension (ICH) is a common cause of death. Much of the intensive care management of patients with ALF is aimed at preventing or treating ICH
    Ventilate to a low normal ETCO2
    Try to avoid high PEEP as it
    can increase ICP and cause hepatic venous congestion
    Keep well sedated
    Assess neurology hourly
    Take standard measures to prevent intracranial hypertension
    Essentially - treat like a TBI, including use of therapeutic hypothermia, bearing in mind that this may worsen coagulopathy. Some centers routinely use therapeutic hypothermia in acute liver failure, and an RCT is underway
  • Lactulose is not routinely indicated
    While useful in early encephalopathy, there is no good evidence to support its use in high grade encephalopathy and it may interfere with fluid balance and make transplant technically more difficult
    Seizures should be treated promptly with a benzodiazepine and phenytoin
    There is no role for prophylactic phenytoin
    Signs of increased ICP such as anisicoria or drop in GCS should be treated with osmotherapy +/- therapeutic hypothermia
  • Limit all fluid intake, Aim for neutral or slightly negative daily fluid balance
    Avoid hypotonic fluids wherever possible
    Avoid nephrotoxins
    Consider Commencing CRRT in all intubated patients, regardless of renal function to reduce ammonia levels and maintain neutral or negative fluid balance
    Aim for a high normal sodium - 145-155
    Hyponatraemia should be treated with HTS
  • Ammonia levels can be monitored and used to stratify risk of intracranial hypertension
    Arterial ideally
    Ammonia <75 = low risk of ICH
    Ammonia >100 = high risk of ICH
    Ammonia >200 = almost certain to have ICH - commence appropriate management
  • Despite an elevated INR being part of the definition of ALF, clinically significant bleeding is rare. This is probably because hepatic production of anticoagulant factors is impaired together with procoagulant factors An elevated INR should not be routinely corrected,
    If the patient is bleeding, used small amounts of FFP to correct coagulopathy, aiming for an INR of <7
    Administer vitamin K
    Keep platelets >10,000/mm3 unless bleeding
  • Bedside tests of coagulation, such as TEG or ROTEM should be used if available, they are much better indicators of the need to treat coagulopathy than traditional tests and can guide the products required.
  • Be vigilant for infection
    Administer broad spectrum antibiotics and an antifungal to all patients with grade III or IV encephalopathy
    There is less evidence for routine antibiotic prophylaxis for patients with a lesser grade of encephalopathy
    Treat fever early and aggressively in order to avoid spikes in ICP
  • - While many patients, particularly those with paracetamol induced ALF will recover with NAC alone, many require OLT. As mentioned earlier, the Kings College Criteria are traditionally used to guide management. Sometimes the liver service will decide not to accept a patient, either because they are too sick and not likely to survive or because they aren’t sick enough. In which case they may remain in the local hospital. It is still wise in this case to stay in touch with the liver service in case of any deterioration
  • - While the KCH criteria are commonly used to prognosticate transplant free survival, others are being investigated. The KCH are the most specific but the least sensitive. Lactate alone is most sensitive but least specific and SOFA has moderate sensitivity and specificity, giving it the highest AUC on a ROC.
  • If a patient is declined by the liver service because they are too sick, they still need meticulous intensive and palliative care at the referring center. The commonest cause of a patient being declined or dying while awaiting transplant is refractory ICH. As with all palliative patients in the ED or ICU, excellent communication with the family and judicious use of analgesia and sedation to ensure comfort and dignity are essential.
  • - Extracorporeal hepatic support relies on a similar principle to CRRT, but aims to clear albumin bound, water soluble molecules (like ammonia) using a variety of albumin based techniques. Biological systems using hepatocytes have also been investigated. Trials have shown mixed results and extracorporeal systems currently have no role outside of the clinical trial setting.
  • So, in summary
    - Find out the cause
    - Call for help
    - Take lots of bloods
    - Give NAC
    - Good housekeeping
    - Get lines in early, including a vascath
    - Treat the high output, vasodilated circulation
    - Treat the brain like a TBI
    - Measure ammonia if you can
    - Start CRRT early
    - Use TEG if you’ve got it
    - Be vigilant for infection
    - Accept that not everyone gets a transplant
    - Provide excellent palliative care to those too sick to transfer
  • BCC4: David anderson on Acute Liver Failure

    1. 1. Acute liver Failure David Anderson Advanced Trainee in Intensive Care Medicine Advanced Trainee in Palliative Medicine
    2. 2. Case
    3. 3. Jaundice Definition Encephalopathy A short time after the onset of Coagulopathy http://www.capitalpath.com.au/about-us/laboratory-information.aspx http://patient.co.uk Encephalopathy
    4. 4. ? Aetiology http://herron.com.au http://giantmicrobes.com http://onlinepillspro.com http://en.wikipedia.org http://indyprops.com
    5. 5. Call for Help http://8774e4voip.com/blog/polycom-soundpoint-ip-bat-phone/
    6. 6. Full Blood Count Biochemistry LFTs Coags (incl fibrinogen) Group and Screen Blood Gas (with Lactate) Paracetamol Level Viral Hepatitis Serologybeta HCG* Ammonia Autoimmune Screen HIV Amylase/Lipase Send Labs http://www.npsg.uwaterloo.ca/people/daniel/rendering/
    7. 7. Give NAC http://nutralife.com
    8. 8. ICU Housekeeping http://allposters.com.au http://mooselicker.wordpress.com/2012/09/24/continuations/
    9. 9. Early Vascular Access http://medgadget.com
    10. 10. Haemodynamics http://lcars47.com http://transfusion.com.au http://hospira.com http://indiamart.com http://healthfirst.com
    11. 11. Encephalopathy http://www.urmc.rochester.edu/hslt/courses/neuroslides/lab2a/slide063.cfm
    12. 12. Encephalopathy ? http://valleyvet.com http://nursingcrib.com http://hexal-elements.de
    13. 13. Start CRRT Early http://gambro.com
    14. 14. Ammonia http://www.luckymojo.com/ammonia.html
    15. 15. Coagulation http://varnerlab.org
    16. 16. TEG Patton et al, 2012 http://www.aacc.org/publications/cln/2011/April/Pages/PlateletFunction.aspx
    17. 17. Microbiology http://giantmicrobes.com
    18. 18. Transplant http://liverfoundation.org.au
    19. 19. Cholongitas et al, 2012 Prognosis
    20. 20. Palliative Care
    21. 21. Extracorporeal Support?
    22. 22. Summary @expensivecare http://expensivecare.com/2013/08/25/alf