From the Guidelines
Acute liver failure requires immediate medical attention in an intensive care unit, with a focus on identifying and addressing the underlying cause, and early consultation with a liver transplant center is crucial for timely intervention. The management of acute liver failure involves a multidisciplinary approach, including critical care and emergency physicians, pharmacists, nurses, advanced practice providers, and dietitians 1. Initial treatment focuses on identifying and addressing the underlying cause, such as discontinuing hepatotoxic medications, administering N-acetylcysteine for acetaminophen overdose, or antiviral therapy for viral hepatitis.
Key aspects of management include:
- Maintaining glucose levels (target 80-120 mg/dL)
- Correcting coagulopathy with vitamin K (10 mg IV daily) and possibly fresh frozen plasma for active bleeding
- Managing cerebral edema with mannitol (0.5-1 g/kg IV) or hypertonic saline (3% solution)
- Controlling infections with prophylactic antibiotics
- Providing nutritional support (35-40 kcal/kg/day) According to the most recent guidelines, liver transplantation evaluation should be initiated promptly for patients with severe encephalopathy or deteriorating liver function despite medical management, as it represents the definitive treatment for many cases 1. The guidelines also emphasize the importance of early recognition and prompt management of liver failure and its complications to improve outcomes 1.
In cases of acetaminophen overdose, N-acetylcysteine should be administered promptly, with a loading dose of 150 mg/kg over 1 hour, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1. The guidelines also recommend that patients with known or suspected acetaminophen overdose within 4 hours of presentation should be given activated charcoal just prior to starting NAC 1. Continuous monitoring of vital signs, neurological status, and laboratory parameters is essential to guide management decisions and ensure timely intervention.
From the FDA Drug Label
Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose Its effectiveness depends on early oral administration, with benefit seen principally in patients treated within 16 hours of the overdose. Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite. Acetylcysteine solution, USP administered orally, is indicated as an antidote to prevent or lessen hepatic injury which may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen. It is essential to initiate treatment as soon as possible after the overdose and, in any case, within 24 hours of ingestion.
The treatment for acute liver failure due to acetaminophen overdose is N-acetylcysteine (IV). It is most effective when administered within 16 hours of the overdose, but treatment should be initiated as soon as possible and within 24 hours of ingestion 2, 2. N-acetylcysteine works by maintaining or restoring glutathione levels or acting as an alternate substrate for conjugation with the reactive metabolite 2.
From the Research
Treatment Options for Acute Liver Failure
- Liver transplantation remains the only chance for cure in those who do not spontaneously recover 3, 4
- Etiologic-specific treatments and supportive measures are routinely employed 3
- Artificial and bioartificial assist therapies may be used as supportive care to allow time for hepatic recovery or as a bridge to liver transplantation, but studies have shown mixed results 3, 4
- N-acetylcysteine (NAC) has been studied as a potential treatment for non-paracetamol-related acute liver failure, but the evidence is inconclusive 5, 6
- Continuous renal replacement therapy (CRRT) and plasma exchange may be considered as important standards of care in managing acute liver failure 7
Management of Acute Liver Failure
- Identifying the cause of acute liver failure is key to guiding specific therapies 7
- Early recognition and proactive intensive management are crucial in reducing the incidence of early neurological death 4
- Close monitoring, regular investigations, and careful attention to neuroprotective measures are essential in managing acute liver failure 7
- Patients should be transferred to a liver transplant centre to achieve the best chance of transplant-free survival, or to undergo emergency liver transplantation if required 7
Role of N-acetylcysteine in Acute Liver Failure
- NAC has been shown to improve survival and reduce mortality in non-acetaminophen-induced acute liver failure in some studies 6
- However, other studies have found inconclusive evidence of the effect of NAC on mortality or transplant rate in non-paracetamol-induced acute liver failure 5
- The use of NAC in acute liver failure is still a topic of debate and requires further investigation 5, 6