What is the management of paracetamol (acetaminophen) poisoning in a pediatric patient with potential liver damage and other health issues?

Management of Paracetamol (Acetaminophen) Poisoning in Pediatrics

All pediatric patients with paracetamol poisoning should receive N-acetylcysteine (NAC) if they meet treatment criteria based on the Rumack-Matthew nomogram, ingestion amount, or evidence of hepatotoxicity—with treatment ideally initiated within 8 hours of ingestion to maximize efficacy and prevent liver failure. 1, 2

Immediate Triage and Risk Assessment

Criteria for Emergency Department Referral

Children under 6 years with repeated supratherapeutic ingestions require immediate ED evaluation if they have ingested: 1

• ≥200 mg/kg over a single 24-hour period, OR
• ≥150 mg/kg per 24 hours for the preceding 48 hours, OR
• ≥100 mg/kg per 24 hours for 72 hours or longer 1

Initial Laboratory Evaluation

• Obtain serum paracetamol level at 4 hours post-ingestion or later (never before 4 hours, as levels cannot be interpreted) 3
• Measure AST, ALT, bilirubin, INR/PT, and creatinine at presentation 2
• If the ingestion time is unknown but paracetamol is detectable, treat immediately 2, 4

Treatment Algorithm Based on Clinical Scenario

Scenario 1: Single Acute Ingestion with Known Time

Use the Rumack-Matthew nomogram to determine treatment need: 1, 2

• Plot the paracetamol level drawn between 4-24 hours post-ingestion
• Treat with NAC if the level plots at or above the "possible toxicity" line (25% below the original "probable toxicity" line) 2, 3
• The nomogram connects 200 mcg/mL at 4 hours to 50 mcg/mL at 12 hours; the treatment line is 25% below this 3

Critical timing considerations: 2

• NAC within 8 hours: only 2.9% develop severe hepatotoxicity
• NAC within 10 hours: 6.1% develop severe hepatotoxicity
• NAC after 10 hours: 26.4% develop severe hepatotoxicity

Scenario 2: Repeated Supratherapeutic Ingestions

The nomogram does NOT apply—use these criteria instead: 1, 2

• Treat with NAC if serum paracetamol ≥10 mg/mL, OR
• Treat if AST or ALT >50 IU/L, OR
• Treat if total ingestion ≥10 g or 200 mg/kg (whichever is less) in 24 hours 5

Special pediatric consideration: Test liver enzymes if a child received >75 mg/kg/day for >24 hours during febrile illness, and treat with NAC if transaminases are elevated 6

Scenario 3: Unknown Time of Ingestion

Treat immediately with NAC if: 2, 4

• Any detectable paracetamol level is present
• AST or ALT are elevated above normal
• History suggests significant ingestion but timing is unreliable

Scenario 4: Delayed Presentation (>24 Hours Post-Ingestion)

The nomogram cannot be used—base treatment on: 2

• Any detectable paracetamol level warrants NAC
• Elevated transaminases (AST/ALT >50 IU/L) mandate NAC
• Start NAC immediately without waiting for confirmatory labs if overdose is suspected 2, 4

Even at 16-24 hours, NAC reduces hepatotoxicity from 58% (untreated) to 41% 2

Scenario 5: Established Hepatotoxicity or Acute Liver Failure

Administer NAC immediately regardless of time since ingestion: 2, 4

• Severe hepatotoxicity defined as AST or ALT >1,000 IU/L 2
• NAC reduces mortality from 80% to 52% in fulminant hepatic failure 2
• NAC reduces cerebral edema from 68% to 40% 2
• Contact liver transplant center immediately 2
• Requires ICU-level care with monitoring for encephalopathy, coagulopathy, renal failure 2

NAC Dosing Regimens

Intravenous Protocol (Preferred in Most Guidelines)

Two-bag regimen (current recommendation): 5

• Loading dose: 200 mg/kg in 5% dextrose over 4 hours
• Maintenance dose: 100 mg/kg over 16 hours
• Total treatment time: 20 hours
• This regimen has significantly fewer adverse reactions than the older three-bag protocol 5

Alternative three-bag regimen: 1, 2

• Loading: 150 mg/kg over 15 minutes
• Second dose: 50 mg/kg over 4 hours
• Third dose: 100 mg/kg over 16 hours
• Total: 300 mg/kg over 21 hours

Oral Protocol (Alternative)

72-hour regimen: 4, 6

• Loading dose: 140 mg/kg orally or via nasogastric tube
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses
• Dilute to 5% solution in juice or soft drink
• May be superior when treatment is delayed 2

Massive Overdose (>30 g or >500 mg/kg)

Increase NAC dosing beyond standard protocol: 2, 5

• Consider step-wise increases for levels plotting at 300-, 450-, or 600-line on nomogram 2
• Paracetamol concentrations more than double the nomogram line require increased NAC doses 5

Adjunctive Therapy

Activated Charcoal

Administer 1 g/kg orally if patient presents within 4 hours of ingestion 2

• Give just prior to starting NAC 2, 4
• Most effective within 1-2 hours but may benefit up to 4 hours 2
• Ensure airway protection, especially with co-ingestions 2
• Do not delay NAC while giving activated charcoal 4

Criteria for Stopping NAC

NAC can be discontinued when ALL of the following are met: 2

• Paracetamol level is undetectable
• AST and ALT remain normal (not just "stable"—must be normal)
• INR is normal
• Patient is asymptomatic

Mandatory extended NAC treatment (beyond standard protocol) for: 2, 4

• Delayed presentation (>24 hours)
• Extended-release formulations 2, 5
• Repeated supratherapeutic ingestions
• Unknown time of ingestion with detectable levels
• Any elevation in AST or ALT above normal
• Rising transaminases
• Any coagulopathy

Continue NAC until transaminases are declining and INR normalizes 2

Special Pediatric Considerations

Modified-Release Formulations

• Serial paracetamol levels required (may show late increases at 14+ hours) 2
• All potentially toxic ingestions (≥10 g or ≥200 mg/kg) should receive full NAC course 5
• Standard dosing applies but monitoring must be extended 4

Intravenous Paracetamol Overdose

• 10-fold dosing errors are relatively common in children 7
• Treat with NAC for overdoses >60 mg/kg 7
• Use caution applying the nomogram to IV overdoses—discuss with poison control 7

Accidental Ingestion in Young Children (<6 Years)

• Most ingestions of pediatric formulations can be managed at home if dose is non-toxic 8
• Less than 5% of children under 6 with toxic plasma levels develop hepatic abnormalities 8
• Orodispersible tablets pose particular risk—children ingest twice the dose compared to other formulations 9

Pregnancy

Treat pregnant adolescents with standard NAC protocols to prevent maternal and fetal toxicity 6

Critical Pitfalls to Avoid

1. Never wait for paracetamol levels to start NAC if there is strong suspicion of significant overdose 4
2. Do not use the nomogram for: 1, 2
   • Repeated supratherapeutic ingestions
   • Unknown time of ingestion
   • Presentation >24 hours post-ingestion
   • Extended-release formulations
3. Low or absent paracetamol levels do NOT rule out poisoning if ingestion was remote or occurred over several days 2
4. Patients may have elevated transaminases despite "no risk" nomogram placement due to inaccurate history or increased susceptibility 2
5. Never stop NAC if any transaminase elevation develops—this mandates continuation until levels are declining 2
6. Chronic alcohol use in adolescents lowers the toxicity threshold to as low as 4 g/day—treat even with "non-toxic" nomogram levels 2

Disposition

• Admit to ICU if: AST/ALT >1,000 IU/L, any coagulopathy, or clinical signs of hepatic failure 2
• Contact poison control for complex cases, unknown timing, or massive overdoses 7
• Psychiatric evaluation mandatory for all adolescent intentional ingestions 8
• Peak enzyme levels expected at 72-96 hours; >99% recover to normal by 7-8 days 8