- Further Management of Acute Liver Failure Before Transfer to a Liver Unit
- Decompensated Chronic Liver Disease
If you suspect ALF:
- Check the blood glucose, as hypoglycaemia is a common complication.
- If <4.0 mmol/L, give 100 mL of 20% glucose or 200 mL of 10% glucose over 15–30 min IV. Recheck blood glucose after 10 min, if still <4.0 mmol/L, repeat the above IV glucose treatment.
- Start an IV infusion of 10% glucose, initially 1L/12h, to prevent hypoglycaemia; use a large peripheral vein as it can cause thrombophlebitis.
- Make a focused clinical assessment (Table 77.2), including a detailed drug history (including any herbal and over-the-counter medications) from the patient or family members, and arrange urgent investigations (Table 77.3).
- If there is any suspicion that ALF is due to paracetamol poisoning, then give N-acetylcysteine (NAC) without delay using the standard regimen (Table 36.9), as this improves outcomes even when given up to 48h after ingestion.
- If there is grade 3 or 4 encephalopathy, transfer the patient to an ICU for elective intubation and ventilation. Other patients with ALF should be nursed in a high-dependency unit.
- Obtain advice on management from a hepatologist or your regional liver unit, with the investigation results to hand when you make the phone call.
Determining the cause of ALF (Table 77.1)Determining the cause of ALF (Table 77.1)
- In the UK, paracetamol poisoning causes around 50% of ALF, and viral hepatitis around 40%. The mortality of patients with paracetamol poisoning who reach medical attention is 0.4%. Where ALF occurs due to viral hepatitis, mortality is around 40% and 60% due to non-A, non-B viral hepatitis.
- Consider mushroom (Amanita phalloides) poisoning in patients with a compatible history; severe nausea, vomiting, diarrhoea and abdominal pain develop within hours to one day of ingestion. Penicillin G 300,000 units/kg/day and milk thistle (silibinin) 30–40 mg/kg/day PO or IV are recognized treatments.
- Wilson's disease and autoimmune hepatitis, although both forms of chronic liver disease, can be treated as if they are ALF. Wilson's classically presents with a Coombs-negative haemolytic anaemia and a high bilirubin to ALP ratio. The diagnosis is confirmed by high urinary copper levels. Treatment aims to lower serum copper levels via haemofiltration. Penicillamine is not recommended acutely. Autoimmune hepatitis should be treated with 40–60 mg prednisolone PO per day.
- The presence of a nodular liver on imaging in a patient suspected of having ALF does not necessarily indicate that the patient has pre-existing cirrhosis. Nodularity can occur with benign conditions. As the severity of fibrosis increases, so, too, does the diagnostic accuracy of ultrasound at detecting cirrhosis. The gold standard for diagnosing cirrhosis is liver biopsy, or non-invasively by a Fibroscan.
- ALF in women in the third trimester of pregnancy is most commonly due to HELLP syndrome (coexistent hypertension and proteinuria) or acute fatty liver of pregnancy (AFLP) (see Chapter 32). AFLP can be confirmed by hepatic steatosis on imaging. Other causes of ALF, however, also occur in pregnancy. Treatment is alongside maternity staff and commonly involves prompt delivery of the foetus.
Further Management of Acute Liver Failure Before Transfer to a Liver Unit
General care and monitoring
- Nurse the patient with 20 head-up tilt in a quiet area of an ICU or high-dependency unit, avoiding unnecessary disturbance.
- Monitor the conscious level, pulse, blood pressure, temperature and plasma glucose 1–4-hourly. Monitor oxygen saturation by pulse oximeter and give oxygen by mask to maintain SaO2 >90%.
- Give platelet concentrate before placing central venous and arterial lines if the platelet count is <50×109/L. Avoid giving fresh frozen plasma (FFP) unless there is active bleeding, as this affects coagulation tests – the best prognostic marker – for several days, and can precipitate fluid overload. If correction of coagulopathy is needed, discuss with your local haematologist: typically FFP is given in combination with recombinant activated factor VIIa.
- If encephalopathy is grade 2 or more, or if systolic BP is <90 mmHg, central venous pressure monitoring and a urinary catheter will be required. Other causes of reduced consciousness need excluding by clinical assessment and CT head. Fluid resuscitation should be with 4.5% human albumin solution or normal saline unless the blood glucose levels are low.
- If encephalopathy progresses to grade 3 or 4, arrange elective intubation and ventilation.
- If there is any evidence of sepsis, then commence antibiotics and antifungals after a full septic screen.
- Give lactulose to assist in ammonia excretion and prevent worsening encephalopathy. Avoid any potentially nephrotoxic agents.
- Put in a nasogastric tube for gastric drainage if the patient is vomiting or is ventilated. Start enteral feeding early or parenteral feeding if required. Replace potassium, magnesium and phosphate as needed (Chapters 86, 88 and 89).
Management of complications
Complications of ALF and management of complications are summarized in Table 77.4.
Cerebral oedema occurs in 75–80% of patients with grade 4 encephalopathy and is often fatal. It may result in paroxysmal hypertension, dilated pupils, sustained ankle clonus and sometimes decerebrate posturing (papilloedema is usually absent). Intracranial pressure (ICP) should be maintained below 25 mmHg. To avoid raised ICP:
- Give mannitol 20% 100–200 mL (0.5–1.0g/kg) IV over 10 min alongside maintenance of mean arterial pressure (MAP) at >75 mmHg using vasopressors, with a cerebral perfusion pressure of 60–80 mmHg.
- Increase plasma sodium to 145–155 mmol/L with hypertonic normal saline (Chapter 85).
- Avoid seizures by using phenytoin alongside short-acting benzodiazepines.
- Consider therapeutic hypothermia 32–34°C as a bridge to transplantation.
Criteria for liver transplantation
These are summarized in Table 77.5.
Search for and treat precipitants (Tables 77.6).
- Spontaneous bacterial peritonitis (SBP) is common and may not be accompanied by abdominal tenderness. If there is ascites, aspirate 10 mL for microscopy and culture (inoculate blood culture bottles). Assume peritonitis is present if ascitic fluid shows >250 white blood cells/mm3, of which >75% are polymorphs, and treat with third-generation cephalosporin, for example cefotaxime 2g 8-hourly IV for 5 days, followed by a quinolone PO for 5 days. See Appendix 24.1 for further discussion of SBP.
- A rectal examination must be performed to exclude melaena. Evaluation and management of acute upper and lower gastrointestinal bleeding is described in Chapters 73 and 74.
Start a liver failure regimen.
- Reduce the intestinal nitrogenous load: start lactulose 30 mL 3-hourly PO until diarrhoea begins, then reduce to 30 mL 12-hourly, adjusted to achieve passage of two soft stools/day.
- Enteral nutrition should be started early to prevent a hypercatabolic state.
- Reduce the risk of gastric stress ulceration: give prophylaxis with omeprazole, ranitidine or sucralfate.
- Maintain blood glucose >4.0 mmol/L. Give dextrose 10% IV infusion initially 1L 12-hourly. Check blood glucose 1–4-hourly and immediately if conscious level deteriorates.
- Fluid and electrolyte balance: the diet should be low in sodium. Give potassium supplements to maintain a plasma level >3.5 mmol/L. If IV fluid is needed, use 4.5% human albumin solution or glucose 5% or 10%. Avoid normal saline. In the absence of renal impairment, treat ascites with spironolactone combined with a loop diuretic if necessary, aiming for weight loss of 0.5kg/day. If ascites is refractory to diuretic therapy, use paracentesis with IV infusion of 100 mL of 20% human albumin solution. See Chapter 24 for further management of ascites.
- Thromboprophylaxis: as patients remain at high risk of venous thromboembolism even when prothrombin time is prolonged, prescribe low-molecular-weight heparin prophylaxis unless there is active bleeding or the platelet count is <50 × 109/L.
- Drugs: give vitamin K 10 mg IV (not intramuscularly) and folic acid 15 mg PO once daily. Avoid sedatives and opioids. Other drugs that are contraindicated are listed in the British National Formulary.
Seek advice on further management from a hepatologist or gastroenterologist.