What are the guidelines for treating paracetamol (Acetaminophen) overdose in pediatric patients?

Acetaminophen Overdose Management in Pediatric Patients

Immediate Treatment Algorithm

All pediatric patients with suspected or confirmed acetaminophen overdose should receive N-acetylcysteine (NAC) immediately if presenting within 24 hours of ingestion, without waiting for laboratory confirmation, as NAC initiated within 8 hours reduces severe hepatotoxicity risk to only 2.9% compared to 26.4% when delayed beyond 10 hours. 1

Initial Interventions (0-4 Hours Post-Ingestion)

• Administer activated charcoal (1 g/kg orally in a slurry) just prior to starting NAC if the child presents within 4 hours of ingestion, as this is most effective within 1-2 hours but may provide benefit up to 4 hours post-ingestion 1, 2
• Do not delay NAC administration while giving activated charcoal—proceed with NAC immediately after charcoal 2, 3
• If the child vomits within 1 hour of activated charcoal or NAC administration, repeat that dose 3

Risk Stratification Using the Rumack-Matthew Nomogram

• Draw acetaminophen level at 4 hours post-ingestion (or as soon as possible if presenting later) and plot on the Rumack-Matthew nomogram to determine treatment need 1
• The nomogram is only valid for single acute ingestions with known time of ingestion, when levels are drawn between 4-24 hours post-ingestion 1
• Treat with NAC if the acetaminophen level plots at or above the "possible toxicity" line (25% below the original "probable toxicity" line) 1
• The treatment threshold is 150 mcg/mL at 4 hours, declining to 50 mcg/mL at 12 hours 3

Pediatric-Specific Dosing Thresholds

• For children weighing less than 70 kg, ingestions of 150 mg/kg or greater represent potentially hepatotoxic doses requiring immediate NAC treatment 3
• A 7g ingestion in a child weighing less than 70 kg represents >100 mg/kg, placing them at higher risk and warranting treatment regardless of nomogram placement 1

NAC Dosing Regimens for Pediatric Patients

Oral NAC Protocol (72-Hour Regimen)

• Loading dose: 140 mg/kg orally or via nasogastric tube 1, 3
• Maintenance dose: 70 mg/kg every 4 hours for 17 additional doses (total 72 hours) 1, 3
• Dilute the 20% NAC solution to 5% concentration using diet cola or other diet soft drinks for oral administration; if using gastric tube, water may be used as diluent 3
• Prepare dilutions freshly and use within one hour 3

Intravenous NAC Protocol (21-Hour Regimen)

• 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

The oral 72-hour protocol may be superior to the 21-hour IV protocol in preserving hepatocytes, particularly when treatment is delayed, though both are effective 1, 4

Special Pediatric Scenarios Requiring Modified Management

Repeated Supratherapeutic Ingestions (Chronic Overdose)

• Treat with NAC if the child received ≥75 mg/kg/day for more than 24 hours during febrile illness and has elevated transaminases (AST or ALT >50 IU/L) 1, 5
• Also treat if serum acetaminophen concentration is ≥10 mg/mL 1
• The nomogram does NOT apply to repeated supratherapeutic ingestions—treatment decisions must be based on acetaminophen levels and liver function tests 1

Accidental Liquid Paracetamol Ingestion in Children

• Liquid formulations may have unpredictable absorption patterns requiring serial acetaminophen levels 6
• Obtain initial level at 4 hours, then repeat at 8 hours to ensure peak has been reached 6

Extended-Release Formulations

• Extended-release paracetamol may show late increases in serum concentration at 14 hours or beyond 1
• Obtain serial acetaminophen levels and continue NAC beyond standard protocol if levels remain detectable or are rising 1, 2

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

• Increase NAC dosing beyond standard protocol for massive overdoses with paracetamol concentrations more than double the nomogram treatment line 1, 6
• Consider step-wise NAC dose increases at the 300-, 450-, and 600-lines on the nomogram 1

When to Continue or Extend NAC Treatment

Standard Stopping Criteria

• NAC can be discontinued when acetaminophen level is undetectable AND liver function tests (AST, ALT) remain normal 1
• Some carefully selected low-risk pediatric patients with normal labs at presentation and 12 hours may safely stop after a 12-hour NAC course, though this requires careful consideration 1

Mandatory Extended Treatment Scenarios

Continue NAC beyond the standard protocol in these situations: 1

• Delayed presentation (>24 hours post-ingestion)
• Extended-release acetaminophen formulations
• Repeated supratherapeutic ingestions
• Unknown time of ingestion with detectable acetaminophen levels
• Any elevation in AST or ALT above normal
• Rising transaminases
• Any coagulopathy (elevated INR/PT)

Critical Red Flags Requiring ICU Care

• If severe hepatotoxicity develops (AST or ALT >1000 IU/L), restart NAC immediately and continue until transaminases are declining and INR normalizes 1
• Children with coagulopathy or AST/ALT >1000 IU/L require ICU-level care and immediate consultation with transplant hepatology 1

Laboratory Monitoring Protocol

Initial Assessment

• Draw baseline labs immediately: acetaminophen level, AST, ALT, bilirubin, prothrombin time/INR, creatinine, BUN, blood glucose, and electrolytes 1, 3

Serial Monitoring

• Repeat AST, ALT, bilirubin, PT/INR, creatinine, BUN, blood glucose, and electrolytes daily if acetaminophen level is in the potentially toxic range 3
• Monitor for complications of acute liver failure including encephalopathy, coagulopathy, renal failure, and metabolic derangements 1

Critical Timing Considerations

The 8-Hour Window

• NAC initiated within 8 hours of ingestion is associated with only 2.9% risk of severe hepatotoxicity 1
• Efficacy diminishes progressively: 6.1% risk when started within 10 hours, 26.4% risk when started after 10 hours 1

Late Presentations (>24 Hours)

• The Rumack-Matthew nomogram does NOT apply to patients presenting >24 hours after ingestion 1
• Administer NAC immediately based on clinical presentation, acetaminophen levels, and liver function tests rather than nomogram placement 1
• Even when started >24 hours post-ingestion, NAC reduces mortality from 80% to 52% in fulminant hepatic failure 1

Common Pitfalls and Caveats in Pediatric Patients

History Reliability Issues

• The reported quantity of drug ingested is often inaccurate and should not guide treatment decisions—always obtain acetaminophen levels 3
• Children may present with elevated transaminases despite being stratified as "no risk" on the nomogram due to inaccurate history or increased susceptibility 1

Persistent Vomiting Management

• If the child vomits any oral NAC dose within 1 hour of administration, repeat that dose 3
• For children persistently unable to retain oral NAC, administer via duodenal intubation or switch to IV route 3
• Diluting NAC minimizes vomiting propensity 3

Activated Charcoal Considerations

• If activated charcoal has been administered, lavage before giving NAC, as activated charcoal adsorbs NAC and may reduce its effectiveness 3
• However, never delay NAC administration even if activated charcoal has been given 2

Unknown Time of Ingestion

• If time of ingestion is unknown but acetaminophen level is detectable, treat with NAC immediately 1
• Obtain a second level 4 hours after the first to determine if peak has been reached 3

Supportive Care Measures

• Maintain fluid and electrolyte balance based on clinical evaluation 3
• Treat hypoglycemia if present 3
• Administer vitamin K1 if prothrombin time ratio exceeds 1.5 3
• Give fresh frozen plasma if prothrombin time ratio exceeds 3.0 3
• Avoid diuretics and forced diuresis 3

High-Risk Pediatric Populations

Children with Risk Factors

• Children with chronic malnutrition, prolonged fasting, or taking enzyme-inducing drugs may develop toxicity at lower doses 2, 7
• Use a lower treatment threshold (treat even with levels in "non-toxic" range) for high-risk children 1, 7

Therapeutic Dosing Concerns

• Even therapeutic doses of 4g/day for 14 days can cause ALT elevations >3 times normal in 31-41% of healthy adults, suggesting children receiving prolonged therapeutic dosing require monitoring 1
• The maximum safe daily dose is 4000 mg, but the FDA recommends limiting combination products to 325 mg per dosage unit 7