What is the recommended dose of N-acetylcysteine (NAC) for acute liver failure in children?

N-acetylcysteine (NAC) Dosing in Pediatric Acute Liver Failure

For pediatric acute liver failure, N-acetylcysteine should be administered intravenously with a loading dose of 150 mg/kg over 15-60 minutes, followed by maintenance doses of 50 mg/kg over 4 hours and 100 mg/kg over 16 hours. 1

Indications for NAC in Pediatric Acute Liver Failure

NAC is indicated in the following scenarios:

• Acetaminophen-induced liver failure: Treatment should be initiated immediately without waiting for serum acetaminophen determinations 2
• Non-acetaminophen liver failure: NAC is suggested to improve morbidity and mortality 2

Administration Routes and Dosing Protocols

Intravenous Administration (Preferred in Acute Liver Failure)

• Loading dose: 150 mg/kg over 15-60 minutes
• First maintenance dose: 50 mg/kg over 4 hours
• Second maintenance dose: 100 mg/kg over 16 hours 1

Oral Administration (If IV access unavailable)

• Loading dose: 140 mg/kg (diluted to 5% solution)
• Maintenance dose: 70 mg/kg every 4 hours for 17 doses 1
• Oral administration may be contraindicated in patients with gastrointestinal bleeding or worsening mental status

Special Considerations for Children

• For children with acute liver failure requiring emergency management, initiate NAC immediately at 1 mg/kg/day 2
• If no improvement is observed or in cases of severe liver failure, the dose can be increased to 2 mg/kg 2
• If there is no response after approximately 1 week of NAC therapy, consideration for hepatic transplantation should be initiated 2
• In cases of persistent severe coagulopathy and/or encephalopathy, transplantation considerations may need to begin after only 2-3 days 2

Monitoring During NAC Treatment

• Monitor for hypersensitivity reactions (occurs in 10-15% of patients)
• Common side effects include nausea, vomiting, and rarely urticaria or bronchospasm 1
• Continue NAC treatment beyond the initial protocol if:
  • Liver enzymes remain elevated
  • INR > 2.0
  • Patient is clinically unstable 1

Efficacy Considerations

• NAC treatment response is usually rapid in acetaminophen-induced liver failure, with urinary SA normalizing after 24 hours and clinical response occurring within 1 week 2
• For non-acetaminophen liver failure in children, evidence is mixed:
  • Some studies show improved survival with native liver 3
  • However, a placebo-controlled trial found that 1-year liver transplant-free survival was significantly lower with NAC (35%) compared to placebo (53%), particularly among children less than 2 years old 4

Adjunctive Management

• Intravenous 10% dextrose/normal saline solutions should be administered at 1.5-2.0 times the normal IV fluid maintenance rate for age to maintain normoglycemia 2
• Consider administration of fresh frozen plasma and vitamin K to correct coagulopathy 2
• Treatment of metabolic acidosis may be required 2
• When the patient is clinically stable, introduce a small amount of complete protein (0.25-0.5 mg/kg/day) by 36-48 hours 2

Important Caveats

• NAC treatment should be initiated as early as possible, as the interval between liver injury and treatment is closely related to outcome 2
• The benefits of NAC may be limited to patients with early-stage encephalopathy (grades I-II) 2
• Consultation with a pediatric liver transplant center should be sought for optimal management 2