What is the recommended dose of acetylcysteine (N-acetylcysteine) for a child with acetaminophen (paracetamol) overdose?

Acetylcysteine Dosing for Pediatric Acetaminophen Overdose

For children with acetaminophen overdose, administer N-acetylcysteine (NAC) using the same weight-based dosing as adults: 140 mg/kg loading dose followed by 70 mg/kg every 4 hours for 17 additional doses (total 72-hour oral protocol), or the 21-hour IV protocol with 150 mg/kg over 15 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. 1, 2

Standard Dosing Regimens

Oral NAC Protocol (72 hours)

• Loading dose: 140 mg/kg orally or via nasogastric tube, diluted to 5% solution 1, 2
• Maintenance doses: 70 mg/kg every 4 hours for 17 additional doses 1, 2, 3
• Preparation: Dilute 20% NAC solution with diet cola or other diet soft drinks to 5% concentration; if using gastric tube, water may be used as diluent 2
• Timing: Freshly prepare dilutions and use within one hour 2

Intravenous NAC Protocol (21 hours)

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 1
• Second dose: 50 mg/kg over 4 hours 1
• Third dose: 100 mg/kg over 16 hours 1

Alternative IV Protocol for Children

A two-stage IV regimen has been studied specifically in pediatric patients and may reduce hyponatremia risk: 4

• Loading dose: 150 mg/kg over 1 hour 4
• Maintenance: 10 mg/kg/hour continuous infusion for 20 hours 4
• Diluent: Use 0.45% NaCl plus 5% dextrose instead of 5% dextrose alone to prevent hyponatremia in children 4

This modified regimen was studied in 40 pediatric patients (mean age 9.5 years, range 3 months to 17 years) with no cases of symptomatic hyponatremia and maintained normal serum sodium levels (mean 140 mmol/L). 4

Treatment Initiation Criteria

Start NAC immediately in children if: 1, 5, 6

• Acetaminophen level plots above the "possible toxicity" line on Rumack-Matthew nomogram (drawn 4-24 hours post-ingestion) 5
• Time of ingestion unknown but acetaminophen level detectable 5
• Evidence of hepatotoxicity (AST or ALT >50 IU/L) with suspected acetaminophen exposure 5
• Any case where acetaminophen overdose is suspected or possible, even without confirmatory history 1, 6

Critical Timing Considerations

Efficacy is time-dependent: 3

• 0-8 hours: Only 2.9% develop severe hepatotoxicity when treated within 8 hours 3
• 8-10 hours: 6.1% develop hepatotoxicity 3
• 10-24 hours: 26.4% develop hepatotoxicity 3
• 16-24 hours: 41% of high-risk patients develop hepatotoxicity (still better than untreated controls at 58%) 3

NAC should still be administered even if >24 hours have elapsed, as it reduces mortality in established liver failure from 80% to 52%. 1, 5

Special Considerations for Children

Activated Charcoal

• Give activated charcoal (1 g/kg) just prior to starting NAC if patient presents within 4 hours of ingestion 1, 5
• If activated charcoal already given, perform gastric lavage before NAC administration 2
• Do not delay NAC while administering activated charcoal 6

Vomiting Management

• If child vomits oral NAC dose within 1 hour of administration, repeat that dose 2
• If persistently unable to retain oral NAC, administer via duodenal intubation 2
• Consider switching to IV route if oral administration repeatedly fails 1

Adverse Reactions

• Oral NAC: Occasional nausea, vomiting, rare urticaria or bronchospasm 1
• IV NAC: Allergic reactions may occur; treat with discontinuation, antihistamines, and epinephrine for bronchospasm 1
• Slow IV infusion rate if itching occurs 1

Massive Overdose Considerations

For very high acetaminophen concentrations, consider increased NAC dosing: 7

• Standard protocol may be insufficient for massive overdoses 7
• Step-wise dose increases suggested at 300-, 450-, and 600-lines on nomogram 7
• A 48-hour IV protocol (140 mg/kg loading, then 70 mg/kg every 4 hours for 12 doses) delivered higher total NAC dose with only 3.4% hepatotoxicity when started within 10 hours 8

Duration of Therapy

Standard 72-hour oral protocol or 21-hour IV protocol should be completed unless: 5, 9

• Acetaminophen level undetectable AND
• AST/ALT remain normal AND
• No risk factors for delayed toxicity (chronic alcohol use, extended-release formulation, repeated supratherapeutic ingestion) 5

Continue or extend NAC beyond standard protocol if: 5

• Delayed presentation (>24 hours post-ingestion) 5
• Extended-release acetaminophen formulation 5
• Repeated supratherapeutic ingestions 5
• Any elevation in AST or ALT above normal 5
• Rising transaminases 5
• Detectable acetaminophen level at end of protocol 5

Common Pitfalls

• Do not wait for acetaminophen levels before starting NAC if strong suspicion exists 2
• Do not use Rumack-Matthew nomogram for repeated supratherapeutic ingestions or presentations >24 hours post-ingestion 5
• Do not assume low/absent acetaminophen levels rule out toxicity if ingestion was remote or occurred over several days 5, 10
• Standard adult dosing applies to children—use weight-based calculations, not reduced doses 1, 2, 4