Acute liver failure

Background

Acute liver failure (ALF) can be defined as the development of coagulopathy and encephalopathy in a patient with previous normal liver function, over a period of <24 weeks. There are over 40 definitions of ALF in the published literature, but virtually all include the development of coagulopathy and encephalopathy. The most common cause of ALF in Europe and North America is paracetamol overdose. Other causes include drug-induced liver injury, autoimmune hepatitis, viral hepatitis, Budd–Chiari syndrome, Wilson’s disease, and pregnancy-induced ALF. In 15% of cases, the diagnosis can be unknown or indeterminate.

Learning outcomes

1 Identify the initial management steps in a patient with fulminant hepatic failure

2 Discuss the challenges in the anaesthetic and critical care management for patients with ALF receiving liver transplantation.

CPD matrix matches

2C04

Case history

A 33-year-old woman (Mrs L) is an inpatient on an acute medical ward, 72 hours following an overdose with 20 g of paracetamol. She did not present until 48 hours after the paracetamol ingestion. You have been asked as the intensive care registrar to assist with sedation, as she is becoming agitated.

What would your initial assessment points be?

◆ ABCD assessment

◆ FBC

◆ Coagulation profile

◆ LFTs

◆ Laboratory and bedside glucose

◆ Paracetamol level

◆ Lactate

◆ Will need a full liver work-up, including hepatitis serology and human immunodeficiency virus (HIV) test.

Case update

An ABCD assessment reveals that she is protecting her airway and has a RR of 24, peripheral oxygen saturations of 98% on air, HR of 130 bpm, BP of 95/40 mmHg, and GCS of 13/15 (E4 M5 V4).

Basic laboratory investigations include:

◆ Hb 100 g/L, WCC 11.2 × 10⁹/L, Plt 45 × 10⁹/L, PT 70 s (INR 5.8), APTT 36 s (APTT ratio 1.2), fibrinogen 0.9 g/L

◆ Na⁺ 137 mmol/L, K⁺ 3.4 mmol/L, urea 12.5 mmol/L, Cr 180 micromoles/L

◆ ALT 28 000 U/L, ALP 150 U/L, Bil 80 micromoles/L, albumin 32 g/L

◆ Glucose 3.1 mmol/L.

Where should she be managed?

◆ She should be managed in an ICU

◆ She should be considered for transfer to a centre with a liver transplantation programme.

At what stage should intubation be considered?

◆ Tracheal intubation should be undertaken before transfer

◆ If already in a transplantation centre, a further period of observation could be considered.

What precautions are necessary around the time of intubation and transfer?

◆ Cerebral oedema is a common cause of death in ALF, and measures to prevent rises in ICP and preserve CPP should be undertaken

◆ A modified RSI technique, including a short-acting opioid, should be used

◆ Patients should be nursed in a neutral 30° head-up position

◆ Tracheal tubes should be taped, rather than tied

◆ Ventilation should aim for a low normal PaCO₂ (4.5 kPa) and avoid hypoxaemia

◆ Hypotension should be avoided; ALF patients are vasodilated, and vasopressor support with noradrenaline is very commonly required.

The patient is intubated, mechanically ventilated, and transferred to the intensive care unit of a centre with a liver transplantation programme. Which criteria can be used to determine whether or not liver transplantation will be necessary?

◆ The King’s College criteria (KCC) may be used

◆ KCC are good at predicting patients with a poor outcome, but less good at predicting those with a good outcome

◆ A full psychiatric assessment would also be necessary prior to listing for liver transplantation.

What should the basic goals of intensive care be in patients with acute liver failure?

◆ Maintain normoxia

◆ Target low-normal PaCO₂ (4.5 kPa)

◆ Maintain MAP >65 mmHg (may need to target higher MAP if intracranial hypertension)

◆ Very likely to need renal replacement therapy: this should be continuous veno-venous haemofiltration (CVVH), not intermittent haemodialysis, for the sake of cardiovascular stability and to prevent large swings in the ICP

◆ Meticulous attention to aseptic precautions and prophylactic antibiotics: sepsis with multiple organ failure is the most common cause of death in patients with ALF

◆ Tolerance of coagulopathy: unless there is frank bleeding or invasive procedures planned, coagulopathy should generally be tolerated, to allow monitoring of liver function. If coagulopathy is profound, advice should be sought from the transplantation centre.

Your patient reaches the King’s College criteria and is listed for a super urgent liver transplantation. Should she have an intracranial pressure monitoring device placed? What are the risks and benefits of this?

◆ The placement of an ICP monitoring device in ALF remains controversial

◆ Cerebral oedema is a common cause of death in ALF, and an ICP monitor may allow treatment strategies to control this

◆ There are risks of precipitating a catastrophic intracranial bleeding during device placement, and correction of coagulopathy prior to this is necessary.

Mrs L has an intracranial pressure monitoring device placed. The opening pressure is 30 mmHg. Which treatments can be used to control her intracranial pressure?

◆ Mannitol

◆ Hypertonic saline

◆ Therapeutic hypothermia

◆ Barbiturate coma

◆ Indomethacin: this has been used in specialist centres as a rescue therapy for refractory raised ICP, though there is limited evidence for this, and it should only be used by clinicians with considerable expertise in managing ALF.

Mrs L receives an offer of a liver within 24 hours of being listed for transplantation. What are the stages of this operation, and what challenges do these present to the anaesthetist?

◆ Major procedure in a critically unwell patient

◆ ICP may be elevated and needs to be controlled intraoperatively

◆ Laparotomy, dissection, and hepatectomy in a coagulopathic patient lead to major blood loss, and massive transfusion is not uncommon

◆ An adequate large-bore central IV access is mandatory

◆ Intraoperative TEG can be utilized to optimize the coagulation status

◆ Patients often have a large vasopressor requirement from the outset, and cardiac output monitoring, such as a pulmonary artery catheter, is usually used

◆ During the anhepatic phase, hypothermia and hypoglycaemia can be severe

◆ When reperfusion of the liver occurs, there can be a massive reperfusion syndrome, manifest as electrolyte abnormalities, arrhythmias, and cardiovascular collapse

◆ K⁺ rises significantly during reperfusion, and, if CVVH has been needed preoperatively, this often needs to be continued intraoperatively. CVVH is more effective in this patient group, as intermittent filtration therapies may be associated with a surge in the ICP.

Mrs L goes on to receive an orthotopic liver transplant. She returns to the intensive care unit after an 8-hour operation. What are the important post-operative considerations?

◆ Ensuring graft function by monitoring PT, lactate clearance, and glucose

◆ Commencement of immunosuppression therapy

◆ A Doppler ultrasound is usually done within the first 24 hours to assess the adequacy of the hepatic artery flow

◆ When the graft appears to be functioning, the patient is normothermic, with a normal acid–base status, consideration can be given to weaning sedation, ventilation, and assessment for extubation.

Case discussion

Any patient with ALF should be discussed with a transplantation centre. In the case of paracetamol overdose, it is vital to ensure that N-acetylcysteine has been administered at the earliest opportunity. Patients with encephalopathy should always be intubated prior to transfer, with precautions taken to prevent rises in the ICP during intubation and transfer. Encephalopathy can deteriorate very quickly, with patients who only appear mildly confused rapidly deteriorating to a comatose state. It is also vital to place an arterial line and central line prior to transfer—shock can develop rapidly and be profound in patients with ALF, necessitating fluid resuscitation and BP support with noradrenaline.

On arrival in a transplantation centre, an assessment will be made as to whether or not the patient is suitable to be listed for orthotopic liver transplantation. The criteria for listing for super urgent liver transplantation in the UK are based on the KCC: arterial pH <7.3 or concurrent grade III/IV encephalopathy, Cr >300 micromoles/L, and PT >100 s. Arterial lactate can now also be used, with a lactate of >3 mmol/L post-fluid resuscitation allowing listing, although there is some debate as to whether the lactate modification adds to the KCC. The decision to list a patient for super urgent liver transplantation requires close interdisciplinary liaison between intensivists, hepatologists, transplant surgeons, psychiatrists, and anaesthetists.

Summary

The survival from ALF has increased dramatically in the transplantation era, from <10% before the 1980s to around 67% now. Predicting which patients can survive without a graft remains a challenge. There are extracorporeal liver support systems available, and future trials may guide the usefulness of this therapy in patients with ALF.