What is the recommended N-acetylcysteine (NAC) infusion dose for pediatric patients with acetaminophen overdose?

N-acetylcysteine (NAC) Infusion Dosing for Pediatric Acetaminophen Overdose

The recommended N-acetylcysteine (NAC) infusion dose for pediatric patients with acetaminophen overdose is a total of 300 mg/kg administered intravenously as three sequential doses: 150 mg/kg loading dose over 15-60 minutes, followed by 50 mg/kg over 4 hours, and 100 mg/kg over 16 hours. 1

Standard Dosing Protocol

The FDA-approved intravenous NAC regimen for pediatric patients follows the same weight-based dosing as adults:

1. Loading dose: 150 mg/kg over 15-60 minutes
2. Second dose: 50 mg/kg over 4 hours
3. Third dose: 100 mg/kg over 16 hours

This regimen delivers a total dose of 300 mg/kg over a 21-hour period. 2, 1

Administration Considerations

Dilution Requirements

NAC is hyperosmolar (2600 mOsmol/L) and must be diluted prior to administration. For pediatric patients, consider the following:

• Dilute in sterile water for injection, 0.45% sodium chloride, or 5% dextrose in water 1
• Adjust osmolarity to a physiologically safe level (generally not less than 150 mOsmol/L in pediatric patients) 1
• Using 0.45% saline with 5% dextrose has been shown to be safe and effective in preventing symptomatic hyponatremia in children 3

Monitoring Requirements

• Monitor for hypersensitivity reactions, which occur in 10-15% of patients 2
• Check hepatic and renal function and electrolytes throughout treatment 1
• Monitor acetaminophen levels, ALT/AST, and INR after the last maintenance dose 1

Alternative Regimens

Some centers have implemented alternative NAC regimens for pediatric patients:

1. Two-stage infusion: 150 mg/kg bolus over 1 hour followed by a continuous infusion of 10 mg/kg/hour for 20 hours (total dose 350 mg/kg) 3

2. Simplified regimen: 150 mg/kg loading dose followed by a maintenance infusion of 15 mg/kg/hour until termination criteria are met 4

These alternative regimens may reduce medication errors and improve patient safety by simplifying administration, but they are not FDA-approved. 4

Treatment Duration Considerations

• Complete the full 21-hour treatment course if there is any uncertainty about the patient's risk of developing hepatotoxicity 1
• Continue treatment beyond the initial protocol if:
  • Acetaminophen levels are still detectable
  • ALT/AST are still increasing
  • INR remains elevated 1

Special Considerations

• For high-risk ingestions (acetaminophen levels >300 mg/L at 4 hours), the standard dose regimen is still effective when started within 8 hours of ingestion 5
• Early administration of NAC (within 8 hours of ingestion) is the most critical factor in preventing morbidity and mortality 2
• NAC treatment should be initiated immediately without waiting for serum acetaminophen determinations in cases of suspected significant overdose 2

Potential Adverse Effects

• Hypersensitivity reactions (rash, hypotension, wheezing, shortness of breath)
• Anaphylactoid reactions (3.4% in pediatric patients) 4
• Use with caution in patients with asthma or history of bronchospasm 1

The standard 21-hour, three-dose regimen remains the most widely accepted protocol for pediatric acetaminophen overdose, with strong evidence supporting its efficacy and safety when administered properly.