What is the recommended dosage of N-acetyl cysteine (NAC) for treating acetaminophen overdose in pediatric patients?

N-Acetylcysteine (NAC) Dosing for Pediatric Acetaminophen Overdose

The recommended N-acetylcysteine (NAC) dosage for pediatric acetaminophen overdose is an oral loading dose of 140 mg/kg followed by maintenance doses of 70 mg/kg every 4 hours for 17 doses, or intravenously with a loading dose of 150 mg/kg over 15-60 minutes, followed by 50 mg/kg over 4 hours and 100 mg/kg over 16 hours. 1

Oral Administration Protocol

For oral administration, follow these steps:

• Loading dose: 140 mg/kg body weight
• Maintenance dose: 70 mg/kg every 4 hours for a total of 17 doses
• Dilute the 20% NAC solution with diet cola or other diet soft drinks to a final concentration of 5% to improve palatability 2
• If the patient vomits within 1 hour of administration, repeat that dose 2
• For patients unable to retain oral medication, consider duodenal intubation or switch to IV administration 2

Intravenous Administration Protocol

For intravenous administration:

• 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

Treatment Initiation and Duration

• Initiate NAC immediately if 24 hours or less have elapsed since acetaminophen ingestion, without waiting for serum acetaminophen determinations 2
• The treatment duration depends on acetaminophen levels and clinical response:
  • If predetoxification acetaminophen level is clearly in the toxic range: complete the full 17-dose regimen (oral) or 21-hour regimen (IV)
  • If acetaminophen level is in the non-toxic range and overdose occurred at least 4 hours before testing: discontinue NAC 2

Special Considerations

Risk Assessment

• Use the Rumack-Matthew nomogram to determine hepatotoxicity risk:
  • Probable risk: >200 mg/L at 4 hours post-ingestion
  • Possible risk: 100-200 mg/L at 4 hours post-ingestion
  • No risk: <100 mg/L at 4 hours post-ingestion 1

High-Risk Populations

• Consider lower treatment thresholds for high-risk patients:
  • Chronic alcoholism
  • Malnutrition
  • Patients on CYP2E1 inducers 1

Monitoring

• Monitor for hypersensitivity reactions (occur in 10-15% of patients)
• Common side effects include nausea, vomiting, and rarely urticaria or bronchospasm
• Monitor hepatic and renal function and electrolytes throughout treatment 1
• Continue NAC beyond the initial protocol if:
  • Elevated liver enzymes persist
  • INR >2.0
  • Patient remains clinically unstable 1

Treatment Efficacy Based on Timing

Early NAC administration significantly improves outcomes:

• When started within 8 hours of ingestion, NAC is protective regardless of initial acetaminophen concentration
• Hepatotoxicity develops in only 6.1% of at-risk patients when NAC is started within 10 hours
• This increases to 26.4% when therapy begins 10-24 hours after ingestion 3

Alternative Regimens

While the standard regimen is well-established, some evidence suggests that shorter courses may be effective in certain cases:

• A retrospective study found that a shorter course (mean 31 hours) of oral NAC was safe and effective in patients who did not show evidence of hepatotoxicity within 36 hours of acute overdose 4
• An alternative IV regimen consisting of a loading dose (150 mg/kg) followed by a maintenance infusion (15 mg/kg/hr) has shown promising results in pediatric patients with comparable safety and efficacy to the standard regimen 5

However, the standard protocol remains the recommended approach based on the most current guidelines, especially for patients with elevated acetaminophen levels or signs of hepatotoxicity.