92  Paracetamol Poisoning

Published

July 2, 2025

92.1 Introduction

Paracetamol (also known as acetaminophen) is one of the most commonly used over-the-counter medications for fever and pain in children. While generally safe at therapeutic doses, paracetamol poisoning can lead to life-threatening hepatotoxicity if taken in excessive amounts.

In Ghana and similar settings, where self-medication and delayed health-seeking behaviors are common, cases of accidental or intentional ingestion are frequently encountered. This makes it essential for every medical student to understand the presentation, pathophysiology, diagnosis, and management of paracetamol poisoning.

92.2 Epidemiology

  • Common cause of drug overdose in children globally.
  • In children under 6, most cases are accidental.
  • In adolescents, intentional ingestion may indicate suicidal ideation.
  • Easy availability and parental unawareness of correct dosing contribute to risk.
  • Liquid formulations (e.g., syrups) and tablets are common sources.

92.3 Toxic Dose

Therapeutic dose:

  • 10–15 mg/kg per dose, up to 60 mg/kg/day in children.

Toxic dose:

  • Single ingestion of ≥150 mg/kg in children is considered potentially toxic.
  • In neonates and infants, even lower doses may cause toxicity due to immature liver metabolism.

92.4 Pathophysiology

Paracetamol is primarily metabolized in the liver by

  1. Glucuronidation and sulfation → Non-toxic metabolites (90%)
  2. Cytochrome P450 enzyme (CYP2E1) → Minor pathway forms a toxic metabolite called NAPQI (N-acetyl-p-benzoquinone imine)

In therapeutic doses

  • NAPQI is rapidly detoxified by glutathione

In overdose:

  • Glutathione stores are depleted
  • NAPQI accumulates → Hepatocellular damage, centrilobular necrosis
  • Severe cases can lead to acute liver failure, coagulopathy, and death

92.5 Clinical Features

Paracetamol toxicity has a four-phase clinical progression:

Phase I (0–24 hours) – Asymptomatic or mild GI symptoms

  • Nausea, vomiting
  • Anorexia
  • Pallor, lethargy
  • Most children appear well

Phase II (24–72 hours) – Hepatic injury begins

  • Right upper quadrant pain or tenderness
  • Elevated liver enzymes (ALT, AST)
  • Prolonged prothrombin time (PT)
  • Oliguria (renal involvement)

Phase III (72–96 hours) – Maximum hepatotoxicity

  • Jaundice
  • Hepatic encephalopathy
  • Bleeding (coagulopathy)
  • Hypoglycemia
  • Acute kidney injury
  • Multi-organ failure

Phase IV (4–14 days) – Recovery or death

  • Complete recovery in survivors
  • Liver regeneration may take weeks

92.6 Risk Factors for Severe Poisoning

  • Delayed presentation (>8 hours)
  • Repeated supratherapeutic dosing
  • Malnutrition (reduced glutathione reserves)
  • Pre-existing liver disease (e.g., hepatitis B)
  • Concomitant use of enzyme inducers (e.g., anti-TB drugs)

92.7 Diagnosis

Clinical history:

  • Time, dose, and formulation of paracetamol ingested
  • Number of tablets or volume of syrup
  • Co-ingestants (e.g., alcohol, antihistamines)
  • Symptoms since ingestion

Physical examination

  • Vital signs, signs of hepatic dysfunction
  • Abdominal tenderness (RUQ)
  • Jaundice, mental status (encephalopathy)

Laboratory investigations:

  • Serum paracetamol level (at 4 hours post-ingestion)
  • Liver function tests (LFTs): ALT, AST, bilirubin
  • Prothrombin time / INR
  • Serum creatinine and urea (renal function)
  • Blood glucose
  • Electrolytes
  • Arterial blood gas (if acidosis suspected)

92.8 Rumack-Matthew Nomogram

Used to interpret serum paracetamol levels and determine need for antidote.

  • Plot serum paracetamol level against time since ingestion (only valid for single acute ingestions)
  • A level above the “treatment line” (150 µg/mL at 4 hours) indicates need for N-acetylcysteine (NAC)

Not applicable for

  • Ingestion <4 hours or >24 hours ago
  • Repeated supratherapeutic ingestion
  • Extended-release formulations

92.9 Management

92.9.1 Initial Stabilization

  1. Airway, Breathing, Circulation (ABCs)
  2. Vital signs monitoring
  3. IV access
  4. Activated charcoal:
    • Indicated if child presents within 1 hour of ingestion
    • Dose: 1 g/kg (maximum 50 g)
    • Only if airway is protected

92.10 Antidote – N-Acetylcysteine (NAC)

Mechanism:

  • Replenishes glutathione stores
  • Enhances non-toxic metabolism of NAPQI

Indications:

  • Serum level above treatment line on nomogram
  • Unknown ingestion time + raised LFTs
  • Clinical signs of hepatotoxicity
  • Suspected ingestion >150 mg/kg

NAC Administration

IV Route (preferred in children):

  • Loading dose: 150 mg/kg over 1 hour
  • Then: 50 mg/kg over 4 hours
  • Then: 100 mg/kg over 16 hours (total = 300 mg/kg over 21 hours)

Oral Route (if IV not available):

  • 140 mg/kg loading dose
  • Then 70 mg/kg every 4 hours × 17 doses (total = 1330 mg/kg over 72 hours)
  • Unpalatable and may induce vomiting

92.11 Supportive Care

  • IV fluids: for dehydration or shock
  • Glucose: to prevent/treat hypoglycemia
  • Vitamin K or FFP: for coagulopathy
  • Dialysis: for renal failure or severe acidosis
  • Liver transplant: in fulminant hepatic failure (not readily available in Ghana)

92.12 Monitoring

  • Liver enzymes every 12–24 hours
  • INR, glucose, renal function
  • Mental status (for encephalopathy)
  • Continue NAC until clinical and biochemical improvement

92.13 Disposition

Scenario Action
Ingestion <150 mg/kg, asymptomatic Observe for 4–6 hours, discharge if well
Ingestion >150 mg/kg, <8 hours ago Begin NAC
Ingestion >24 hours ago, symptomatic Treat as hepatic injury, give NAC
Intentional overdose Admit, psychiatric evaluation

92.14 Prevention Strategies

  • Public education: About correct pediatric dosing
  • Child-proof containers
  • Proper labeling of medications
  • Avoid overlapping medications with paracetamol content (e.g., cold and pain meds)
  • Educate parents to seek medical attention early after overdose

92.15 Special Considerations in Ghana

  • Limited access to serum paracetamol assays: clinical judgment and reported dose guide treatment
  • NAC may not always be readily available – advocate for stocking in district and regional hospitals
  • Traditional medicines may contain unknown paracetamol content – careful history is important
  • Early transfer to higher-level facilities for severe cases
  • Community education on risks of overmedication and self-medication

92.16 Case Scenario

Case 1: 3-year-old girl

Presentation:

  • Mother reports child accidentally drank 10 teaspoons of paracetamol syrup (120 mg/5 ml) ≈ 1200 mg
  • Weight: 12 kg → Toxic dose = 1800 mg (150 mg/kg)
  • Child appears well; ingestion occurred 2 hours ago

Action:

  • Calculate dose: 1200 mg ÷ 12 kg = 100 mg/kg
  • Below toxic threshold → Observe for 4–6 hours
  • No NAC needed
  • Educate mother on correct dosing

Case 2: 13-year-old girl (suicidal ingestion)

Presentation:

  • Took 20 x 500 mg tablets (10,000 mg) 4 hours ago
  • Weight: 40 kg → Dose = 250 mg/kg (toxic)
  • Nausea, abdominal pain
  • Start IV NAC
  • Check LFTs, INR, glucose
  • Admit and arrange psychiatric evaluation

92.17 Summary Table

Parameter Value
Safe dose 10–15 mg/kg/dose
Maximum daily dose 60 mg/kg/day
Toxic dose >150 mg/kg (single ingestion)
Antidote N-acetylcysteine (NAC)
NAC IV dose 300 mg/kg over 21 hours
Serum level interpretation Rumack-Matthew nomogram
Onset of liver injury 24–72 hours post-ingestion
Outcome Excellent if treated early

92.18 Conclusion

Paracetamol poisoning is common, preventable, and potentially fatal if not recognized and treated early. Prompt administration of N-acetylcysteine can prevent liver failure even in significant overdoses. In Ghana, clinical assessment remains the cornerstone due to limited laboratory resources. Medical students must be vigilant, advocate for early treatment, and educate caregivers on safe medication practices.