Clinical Manifestations of Acetaminophen Overdose in Pediatric Patients
Children who ingest more than 150 mg/kg of acetaminophen typically progress through four distinct clinical stages, though pediatric patients under 6 years demonstrate markedly less hepatotoxicity than adults and adolescents. 1, 2
Stage-Based Clinical Presentation
Stage I (0–24 hours post-ingestion)
- Nausea, vomiting, diaphoresis, and anorexia beginning 7–14 hours after ingestion 1
- Pallor and malaise are common early findings 2
- Many children remain asymptomatic during this window, particularly those under age 6 2
- Mental status changes should prompt evaluation for co-ingestants rather than acetaminophen alone 2
Stage II (24–48 hours post-ingestion)
- Initial symptoms may diminish, creating a false sense of improvement 1
- AST, ALT, bilirubin, and prothrombin time begin to rise 1
- Patients often report feeling better despite evolving laboratory abnormalities 2
- Right upper quadrant abdominal tenderness may develop 3
Stage III (72–96 hours post-ingestion)
- Peak hepatotoxicity occurs during this window 1, 2
- AST levels can reach 20,000 IU/L in severe cases 1
- Severe hepatotoxicity is defined as AST or ALT >1,000 IU/L 4
- Coagulopathy manifests as prolonged prothrombin time 1
- Jaundice becomes clinically apparent 2
- Hepatic encephalopathy may develop in fulminant cases 5
Stage IV (4 days to 2 weeks post-ingestion)
- Complete recovery occurs in over 99% of treated pediatric patients by 7–8 days 2
- Resolution of transaminase elevations to normal values 2
- Long-term hepatic sequelae are not expected in survivors 2
Critical Age-Related Differences in Pediatric Toxicity
Children under 10–12 years follow a distinctly different pattern with significantly less hepatotoxicity than adults. 1
- Less than 5% of children under age 6 with toxic plasma levels develop transient hepatic abnormalities 2
- Young children demonstrate only minor transaminase elevations compared to adults with equivalent exposures 1
- No deaths occurred in children under 6 years in the landmark Smilkstein study when treated appropriately 6
High-Risk Presentations Requiring Immediate Recognition
Repeated Supratherapeutic Ingestion (RSTI)
- Symptoms are often nonspecific, leading to delayed diagnosis 7
- Patients with AST 50–1,000 IU/L have 15% hepatotoxicity risk and 2% mortality 6
- Those with AST >1,000 IU/L face 14% mortality 6
Delayed Presentation (>24 hours)
- Diagnosis and treatment are more likely to be delayed in unintentional cases 7
- Treatment delays beyond 10 hours result in 53% severe hepatotoxicity with 5% mortality 6
- All 11 deaths in the Smilkstein cohort occurred in patients treated >10 hours post-ingestion 4
Red Flag Symptoms Mandating Emergency Evaluation
- Repeated vomiting beyond the initial 24-hour window 3
- Right upper quadrant abdominal tenderness 3
- Mental status changes (though this suggests co-ingestion) 3, 2
- Any hepatic symptoms (fatigue, jaundice, confusion) developing after 24 hours 8
Common Diagnostic Pitfalls
- Asymptomatic presentation does not exclude toxicity—many children remain well-appearing during Stage I 2
- Improvement at 24–48 hours is expected and does not indicate resolution; this is the characteristic Stage II "latent period" 1
- Unintentional overdoses present later because symptoms are nonspecific and caregivers may not recognize acetaminophen exposure 7
- Therapeutic doses (≤75 mg/kg/day) rarely cause hepatotoxicity in children under 6 years, with only 6 validated cases of hepatic abnormalities at therapeutic dosing 9