What is the best course of management for a patient with suspected acute liver failure?

Management of Suspected Acute Liver Failure

Immediately initiate N-acetylcysteine regardless of etiology, provide aggressive hemodynamic support with albumin-based resuscitation, administer empirical broad-spectrum antibiotics at first sign of clinical deterioration, and urgently transfer to a liver transplant center for evaluation, as liver transplantation is often the only lifesaving option. 1

Immediate Pharmacologic Intervention

• Start N-acetylcysteine (NAC) immediately without waiting for diagnostic confirmation or etiology determination, as it improves transplant-free survival and post-transplant survival even in non-acetaminophen acute liver failure 1, 2
• NAC reduces progression to grade III-IV encephalopathy and mortality 1
• The loading dose should be administered as per FDA labeling: 300 mg/kg total given intravenously as 3 separate sequential doses over 21 hours 2

Hemodynamic and Circulatory Management

• Use albumin as first-line fluid resuscitation rather than crystalloid, with all solutions containing dextrose to maintain euglycemia 1
• Target mean arterial pressure (MAP) ≥50-60 mmHg through aggressive fluid resuscitation first 1
• If fluid replacement fails, initiate vasopressors: norepinephrine is recommended as first-line vasopressor 3
• Consider vasopressin as second-line agent when increasing doses of norepinephrine are required 3
• Perform bedside echocardiography to evaluate volume status and cardiac function, as some patients develop right or left cardiac dysfunction 3
• Consider screening for adrenal insufficiency or empiric trial of hydrocortisone 50 mg IV every 6 hours (or 200-mg infusion) for refractory shock requiring high-dose vasopressors 3

Infection Prevention and Management

• Administer empirical broad-spectrum antibiotics immediately if there are signs of worsening encephalopathy or systemic inflammatory response syndrome—do not wait for culture results 1
• Bacterial infections occur in 60-80% of acute liver failure patients and fungal infections occur in one-third 3, 1
• Broad-spectrum antibiotics should cover common organisms such as enterobacteria, staphylococcal or streptococcal species 3

Airway and Ventilation Management

• Perform tracheal intubation when Glasgow Coma Scale <8 3, 1
• Use protective mechanical ventilation settings per critical care guidelines 3
• Avoid high PEEP levels (>10 cmH₂O) due to risk of hepatic congestion 3, 1

Metabolic and Electrolyte Management

• Monitor blood glucose at least every 2 hours and maintain normoglycemia with continuous glucose infusions and insulin therapy, as hypoglycemia can mimic hepatic encephalopathy 3, 1
• Target serum sodium between 140-145 mmol/L 3, 1
• Correct sodium abnormalities no faster than 10 mmol/L per 24 hours 3, 1
• Monitor and correct electrolyte disturbances, particularly serum phosphate 3

Coagulation Management

• Do not routinely correct coagulation abnormalities 3, 1
• Restrict clotting factor administration to active bleeding or high-risk invasive procedures only 3, 1
• Prophylactic administration of coagulation factors precludes assessment of disease evolution and is not supported by evidence 3
• A recent multicentre study of 1770 ALF patients reported bleeding complications in only 10%, with 1.5% post-procedural bleeding 3

Renal Replacement Therapy

• Regional citrate anticoagulation should be monitored because of potential metabolic effects in patients with ALF 3
• Consider early renal replacement therapy in appropriate clinical contexts 1

Hepatic Encephalopathy and Intracranial Pressure Management

• Avoid benzodiazepines for sedation, as they worsen encephalopathy 3
• Protocol-based sedation to minimize depth and duration reduces morbidity and mortality 3
• Use dexmedetomidine with caution, as its metabolism is exclusively hepatic 3
• Regular monitoring of patients with high-grade encephalopathy (grades 3 and 4) is essential 3
• Transcranial Doppler ultrasound is a useful first-line monitoring tool for intracranial pressure 3
• ICP monitoring devices have been associated with hemorrhagic complications (7-20% of cases) and have not demonstrated mortality benefit 3
• Do not use osmotic laxatives (lactulose) or non-absorbable antibiotics (rifaximin) to lower ammonia levels, as this is not recommended 3

Liver Support Systems

• Extracorporeal liver support systems (MARS, Prometheus) do not improve survival and should not be recommended 3
• These techniques should not delay transfer to a liver transplantation center 3

Urgent Liver Transplantation Evaluation

• Evaluate urgently for liver transplantation as this is often the only lifesaving option, particularly when transplant-free survival is <25% 1
• Post-transplant survival rates for acute liver failure are 80-90% 1
• Early referral to a transplant center is critical as the "transplantation window" is often narrow 1
• Patients should be treated in intermediate care or intensive care settings at a transplant center 3

Additional Supportive Measures

• Stress ulcer prophylaxis is usually recommended in this at-risk population 3
• Monitor hepatic and renal function and electrolytes throughout treatment 2
• Organ function (liver, kidney, brain, lung, coagulation, circulation) should be monitored frequently and carefully throughout hospitalization, as ALF is a dynamic condition 3

Critical Pitfalls to Avoid

• Do not delay NAC administration waiting for etiology confirmation 1
• Do not delay antibiotic administration waiting for culture results 1
• Do not delay transfer to transplant center, as late referral may make transplantation impossible due to rapid evolution 3
• Do not routinely correct INR/coagulopathy, as this prevents assessment of disease progression 3
• Do not use benzodiazepines for sedation in patients with encephalopathy 3