Welcome back to the tasty morsels of critical care podcast.

Today we’re going to try and cover the not insubstantial topic of acute liver failure from Oh’s Manual chapter 44. As you can imagine this will be a superficial skim of the topic so set your expectations appropriately.

First point is differentiating acute from acute on chronic liver failure. This has a massive impact on presentation, diagnosis and management and I must confess for many years as a trainee my understanding of the distinction between the two was a little cloudy and it was only really in fellowship that it became clear to me.

Oh describes it as a massive parenchymal liver injury with multi system impact and organ failure. Coagulopathy and encephalopathy with various degrees of hypotension and renal failure are the main presentations. Encephalopathy and coagulopathy are needed to make the diagnosis. This happens in the context of a previously normal liver.

Acute on chronic liver failure occurs when someone with pre-existing liver disease eg cirrhosis has a decompensation. This may be a consequence of portal hypertension like bleeding or encephalopathy or sometimes it’s infection. Encephalopathy may or may not be a part of it. Portal hypertension is a substantial feature whereas it is typically absent in acute liver failure.

So what we’re expecting to see to make a diagnosis of acute liver failure in the critical care environment is a patient with what is thought to be a previously normal liver present with a rapid progression of symptoms and jaundice leading to encephalopathy. Now “acute” can be within 6 weeks from jaundice to encephalopathy but they’re not typically the type of patients that come to us.

The rapid outpatient to ICU trajectory is typically within days and a differential arranged by prevalence in the western world should include

• paracetamol
  • the commonest and is not always obvious and can be large single overdose or a staggered intentional overdose or even a therapeutic misadventure on the ward in someone with a low BMI
• idiopathic
  • while a common end point of the work up it is not a helpful diagnostic category
• drugs
  • idiosyncratic reactions to any number of medications including things as simple co amoxiclav or an NSAID
• viral
  • these are the alphabet soup of hepatitides. This is no doubt commonest world wide but is much less likely in our part of the world. The tests should definitely be sent but don’t expect much
• autoimmune
• vascular
  • the commonest liver injury we see is usually ischaemic as part of sometihng like OOHCA. But usually it’s not the liver on its own that causes the mortality as the brain injury usually kills them first
  • portal vein thromboses and budd chiari (blockage of venous outflow) do happen and why the imaging is important
• Heat related
  • • we’ve had a couple of these in the past few years related to exertional heat injury. The context is obvious and the care largely supportive
• pregnancy
  • HELLP syndrome and acute fatty liver of pregnancy fall under this banner
• mushrooms
  • i have never looked after an amanita poisoning but they do exist in Ireland. You are orders of magnitude more likely to get in trouble with paracetamol than mushrooms but you should still keep mushrooms on your list.

When investigating this there is a long list of labs that should be sent but beyond the routine labs you get on anyone you should check for the hepatitis viruses, have a look at eosinophil count if you’re thinking about drug reactions and if you really are unsure then they all end up getting urinary copper and ceruloplasmin to look for Wilson’s. Imaging with either US or more likely US and CT is important. Liver biopsy is often indicated but it is disappointing in it’s yield and comes with bleeding complications

Encephalopathy is assessed with a specific 4 level grading system known either as the West Haven or Parson’s Smith scale. Grades 3-4 is where we’re likely to get involved. There are multiple reasons for the encephalopathy – ammonia is obviously part of it but there are other factors involved. Ammonia is taken up by astrocytes and deamination to glutamine  which in turn draws in water leading to astrocyte swelling. In addition there is likely loss of autoregulation and integrity of the blood brain barrier as part of inflammatory response to acute liver injury. Ultimately this means that these patients are at risk of an ICP crisis (unlike acute on chronic liver failure where the brain has been able to compensate). The ICP crisis can be a real source of morbidity and mortality and all of our usual arsenal of ICP management strategies have been employed in supporting these patients.

The coagulopathy is often profound in terms of the numbers measured. Thombocytopaenia is typically consumptive. The INR is prognostic and correcting it routinely does not seem of much benefit. Indeed we should remember that levels of both pro and anticoagulant factors are depressed though we only measure the procoagulant ones typically. As a result the coagulopathy may have a degree of balance to it that we simply don’t measure. Surgical procedures probably need attempted correction of coagulopathy but simple things like CVC insertion are probably safe.

NAC is a truly life saving and effective drug in paracetamol overdose and should be used liberally. It is unclear how helpful it is in other forms of liver failure but given its benign side effect profile it is used early and liberally and a decision to give some should not be something to spend too much time on.

Kidney injury is common but we should probably be filtering earlier than we might conventionally do so. The idea is that CRRT can wash the blood of some of the foul humors that the liver isn’t dealing with. The dose of CRRT here is typically a lot higher at 45ml/kg or higher rather than our usual 25. This has a limited evidence base but it is published on and frequently used.

On a similar vein (pun intended) of removing evil humors, plasma exchange has been used and a small open label RCT exists.

An SAQ or viva may raise the existence of MARS – Molecular Absorbent Recirculating System. This was thought of as “liver dialysis” but does not seem to have panned out and does not seem to be in regular use

Finally it is critical to consider liver transplant as an option for these patients. Unlike in heart or lung transplant where you need a stable patient with limited organ failures to be a candidate, in acute liver failure you can be in the throes of severe multiorgan failure and still be a candidate for liver transplant. Hopefully your liver physicians will have made the referral for you but if not you should be making the phone call.

Reading

Oh chapter 40

Larsen, F. S. et al. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol 64, 69–78 (2016).