For some reason, the college has decided to ask about this esoteric branch of transplant ICU on three separate occasions, with two identical questions:

It is difficult to determine exactly why this might have happened. One interpretation might be the fascinating physiology of the anhepatic patient, and the need to consider all the missing functions of the liver which one might need to support perioperatively. Assessment drives learning and preparing for the liver transplant SAQ would force the exam candidates to explore the topic of severe acute liver failure, an area which presumably would otherwise somehow go neglected. However, one might point out that the same could be achieved by asking a question about acute fulminant hepatitis due to the inadvertant ingestion of Amanita phalloides , or the much more common acute ischaemic hepatitis following cardac arrest, or a viral hepatitis, or something similar. Adult liver transplantation specifically is something performed at only five hospitals in Australia: RPAH in Sydney, The Austin in Victoria, Princess Alexandra in Brisbane, Flinders in Adelaide and Sir Charles Gardiner  in WA.  According to transplant.org 264 only liver transplants happened in Australia in 2015. As such, only a minority of the trainees will ever have any exposure to the process, as these units might only account for no more than 5% of the total training positions. Because of the pyramidal structure of the ICU medical hierarchy, the number of fully qualified specialists  who would ever have to manage such a patient is even smaller. This makes the examiner's fascination with liver transplantation all the more puzzling, as being intimately familiar with it is clearly not something that discriminates a safe ICU specialist from an unsafe one. However, they keep asking these SAQs; and therefore the savvy CICM Part II candidate from a small regional centre still  needs to become familiar with this topic in the event that it ever appears again in the written paper.

Intraoperative fluid management

This is somewhat tricky. Usually, liver transplantation is accompanied by torrential blood loss. And as you keep filling the central compartment, it all leaks out again. Clearly, some sort of intelligent hemodynamic monitoring strategy is the key to success, with gradual incremental fluid and blood product replacement.

The stages of a liver transplant are traditionally called the "preanhepatic", "anhepatic" and "neohepatic" or "reperfusion" phases. Traditionally, the anhepatic phase of transplantation has been managed with an artifically low CVP (0-5mmHg). This prevents excessive blood loss from venous anastomotic sites as well as decreasing graft congestion. One good free article on this topic suggests that this is probably a bad idea on the grounds of increased renal morbidity, whereas another similar article supports this practice on the grounds of improved post-operative graft function. This is a fight among anaesthetists and one would be well advised to stay out of it. The pragmatic intensivist will merely want to know which war camp was in charge of anaesthetising their patient, to prepare for the ensuing renal failure.

Lastly, the "reperfusion" phase of the transplant is characterised by wild haemodynamic instability, as vasoactive products of anaerobic metabolism are flushed out of the donor liver by the first pulses of the recipient's blood. This could last all of 5 minutes, or it could last for many hours, well into their ICU stay. In this situation, one can manage things as if it were a SIRS response, using vasopressors.

Postoperative complications

The post-operative period is peppered by early complications, which are usually the only sort the intensivist will get to see. This has been well summarised in an excellent article from The Annals of Hepatology. I have added using Oh's Manual to form the table below:

Respiratory complications:

  • Right hemidiaphragm paralysis
  • Portopulmonary hypertension
  • Pleural effusion

Circulatory complications:

  • Profound hypotension
  • Massive hypertension

Neurological complications:

  • Hepatic encephalopathy
  • Seizures
  • Intracranial haemorrhage
  • Central pontine myelinolysis

Metabolic complications

  • Hypoglycaemia
  • Lactic acidosis
Renal complications
  • Acute renal failure (ATN)
  • Hepatorenal syndrome
  • Tacrolimus toxicity
  • Intra-abdominal hypertension

Graft-related complications

  • Primary graft non-function
  • Acute and hyperacute rejection
  • Graft infection and sepsis
  • Hepatic artery thrombosis
  • Portal vein thrombosis
  • Biliary leak
  • Perigraft haemorrhage

Respiratory complications

There are several specific lung-related problems which occur following liver transplantation:

  • Right hemidiaphragm paralysis due to phrenic nerve palsy - this is usually a self-limiting neuropraxia which resolves rather rapidly. It happens because the phrenic nerve gets caught in the vice when the suprahepatic portion of the inferior vena cava gets clamped.
  • Portopulmonary hypertension may still be happening and this will take a year to resolve. However, you can't wait for that. Perfusion of the graft will be compromised if right heart failure causes graft congestion. Ergo, a vigorous treatment of pulmonary hypertension needs to be carried out, and Oh's Manual suggests that the approach to this does not need to be substantially different from the normal approach to primary pulmonary hypertension (eg. sildenafil, bosantan, etc etc)
  • Pleural effusion is the most common complication, and occurs for a huge variety of reasons, not the least of which is the persisting hypoalbuminaemia and vigorous fluid resuscitation.

Circulatory complications

Two things could go wrong with the cardiovascular system:

  • Profound hypotension due to reperfusion syndrome (or maybe haemorrhage)
  • Massive hypertension due to reversal of nitric oxide synthase hyperactivity; and on top of that the calcineurin inhibitors (eg. tacrolimus) have a well-known prohypertensive effect.

These are managed without any transplant-specific strategies; vasopressor or vasodilator titration is no different.

Central nervous system disturbances

The central nervous system gets hit as badly as every other organ system.

  • Hepatic encephalopathy probably pre-dates the transplant, and takes some time to resolve. If the intracranial pressure was elevated, it may take a couple of days to return to normal.
  • Seizures may develop due to the calcineurin inhibitors
  • Intracranial haemorrhage may complicate the situation, especially as the patient has wildly fluctuating blood pressure, and is profoundly coagulopathic.
  • Central pontine myelinolysis may result from uncautious use of sodium-containing resuscitation fluids in a cirrhotic patient with chronic hyponatremia.

Electrolyte and acid-base derangement

Metabolic and electrolyte abnormalities may develop, but to which extent is largely determined by graft health. These complications include:

  • Hypoglycaemia
  • Lactic acidosis

Renal failure after liver transplant

Renal failure may complicate the recovery, as a result of

  • ATN due to intraoperative hypotension
  • Exacerbation of preexisting hepatorenal syndrome
  • Toxic effects of calcineurin inhibitors
  • Intra-abdominal hypertension and abdominal compartment syndrome

Graft-related catastrophes

The graft itself could be the source of major problems:

  • Primary graft non-function: it just fails to work, from the very beginning.
    • This sort of patient behaves as if they have no liver whatsoever.
    • Early retransplantation is usually the only solution
  • Acute and hyperacute rejection tends to occur 5-7 days post transplant. There is the "hyperacute" variety, which happens within the first 10 days, and the "acute" variety, which takes up to 7 days to develop.Both are characterised by progressive LFT derangement and fever. One may wish to exclude sepsis before one gives pulsed methylprednisone.
    • Hyperacute rejection is rapid in onset, and characterised by coagulopathy and acidosis.
    • Acute rejection is usually associated with RUQ pain and high bilirubin, but the coagulation system remains intact.
  • Graft infection and sepsis generally are common. Bacterial infections are the most likely in the first few weeks; thereafter, one must consider viruses (eg. CMV), protozoa eg. Toxoplasma and fungal pathogens. CMv is of particular interest: it is the single most common opportunistic infection in solid organ transplant recipients. The third week post transplant is the most likely time it will strike. IV ganciclovir seems to be the drug of choice. Additionally, hepatitis C and B viruses can be reactivated by the steroid immunesuppression.
  • Hepatic artery thrombosis tends to be announced by a massive and sudden rise in the transaminase enzymes. Its pretty uncommon (1.5% of cases) but of these unlucky few, the majority (50-70%) will require retransplantation, because by the time you find out about it the graft has already been irreversibly damaged.
  • Portal vein thrombosis is also pretty rare, and also associated with a rather high rate of retransplantation. Again, the usual way you discover this is by a sudden rise in LFTs. Portal hypertension and ascites take a little time to develop. Varices - if they exist - an usually they do - will again become engorged with blood, and may bleed torrentially.
  • Biliary leak is the scourge of the liver transplant surgeon. The bile duct blood supply is fragile (only the hepatic artery supplies it after transplantation) and it becomes vulnerable to ischaemia. I the split grafts, the cut surface of the liver is a rich leaky source of bile. The bile can leak and slosh all over the abdomen causing a nasty peritonitis, or it can form a bilioma, or the bile duct may block totally and cause cholangitis.
  • Perigraft haemorrhage is actually not as common as one would expect given the situation, and tends to lead to reoperation only in 10-15% of cases. In these situations, a conservative approach may be the most appropriate - much of the time it will be self-limiting if coagulopathy is corrected.

References

Chapter 101  (pp. 1040)  Liver  transplantation by Anish  Gupta,  Simon  Cottam  and  Julia  Wendon

Roberts, Mark S., et al. "Survival after liver transplantation in the United States: a disease‐specific analysis of the UNOS database." Liver transplantation 10.7 (2004): 886-897.

Onaca, Nicholas N., et al. "A correlation between the pretransplantation MELD score and mortality in the first two years after liver transplantation." Liver transplantation 9.2 (2003): 117-123.

Vaid, Arjun, et al. "Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis." ASAIO Journal 58.1 (2012): 51-59.

Bañares, Rafael, et al. "Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute‐on‐chronic liver failure: The RELIEF trial." Hepatology 57.3 (2013): 1153-1162.

Schroeder, Rebecca A., et al. "Intraoperative fluid management during orthotopic liver transplantation." Journal of cardiothoracic and vascular anesthesia 18.4 (2004): 438-441.

Kirby, R. M., et al. "Orthotopic liver transplantation: postoperative complications and their management." British journal of surgery 74.1 (1987): 3-11.

Hannaman, Michael J., and Zoltan G. Hevesi. "Anesthesia care for liver transplantation."  Transplantation Reviews 25.1 (2011): 36-43.

Moreno, Rosalba, and Marina Berenguer. "Post-liver transplantation medical complications."  Ann Hepatol 5.2 (2006): 77-85.

McCaughan, Geoffrey W., and Stephen R. Munn. "Liver transplantation in Australia and New Zealand." Liver Transplantation 22.6 (2016): 830-838.