Doctors Revision

Toxicology / Poisoning

Paracetamol Poisoning

Poisoning due to ingestion of excessive amounts of paracetamol (acetaminophen). Toxic dose typically >150 mg/kg or >7.5 g total in adults (children <6y: 200 mg/kg). Can cause severe, potentially fatal, delayed liver damage (hepatotoxicity) if not treated promptly with the antidote N-acetylcysteine (NAC).

Also known as: Acetaminophen Poisoning, Paracetamol Overdose, PCM Overdose

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Referral and warning signs

When to refer

ALL patients with suspected paracetamol overdose potentially requiring NAC treatment MUST be referred urgently to Hospital (H/RR). This includes those with: Paracetamol level above the treatment line on the nomogram. History of ingesting a potentially toxic dose (>150mg/kg or >7.5g) presenting >8h post-ingestion or with unknown timing/staggered dose. Any evidence of liver injury (elevated LFTs, jaundice) or other complications (AKI, encephalopathy, coagulopathy). Need for IV NAC infusion and monitoring.

Red flags

  • Paracetamol level plotting above the treatment line on the nomogram
  • Jaundice
  • Right Upper Quadrant (RUQ) tenderness
  • Confusion, lethargy, or altered mental status (hepatic encephalopathy)
  • Elevated INR (> 1.5) or signs of bleeding
  • Rising creatinine or oliguria (acute kidney injury)
  • Significant elevation of AST/ALT (e.g., >1000 IU/L)
  • Metabolic acidosis
  • Hypoglycemia

Signs and symptoms

  • Phase 1 (0-24 hours): Often asymptomatic or mild, non-specific symptoms: Nausea, vomiting, malaise, anorexia, pallor, diaphoresis.
  • Phase 2 (24-72 hours): Initial symptoms may improve, but liver injury begins. Development of Right Upper Quadrant (RUQ) abdominal pain, liver tenderness. Liver enzymes (AST, ALT) start to rise.
  • Phase 3 (72-96 hours): Peak hepatotoxicity. Jaundice, worsening RUQ pain, hepatic encephalopathy (confusion, lethargy, coma), coagulopathy (prolonged INR, bleeding), hypoglycemia, metabolic acidosis (lactic acidosis), acute kidney injury (may occur with or without liver failure).
  • Phase 4 (>4 days / 96 hours): Either resolution phase with gradual recovery (liver regeneration over days/weeks) OR progression to fulminant hepatic failure, multi-organ failure, and death.

Risk factors

  • Intentional overdose (most common cause of severe poisoning).
  • Accidental overdose: Therapeutic misadventure (e.g., taking multiple different paracetamol-containing products concurrently, incorrect dosing esp. in children, using adult formulations for children).
  • Staggered overdose (supratherapeutic ingestion over >24 hours).
  • Factors increasing susceptibility to toxicity at lower doses: Chronic alcoholism (depletes glutathione), Malnutrition/fasting state, Use of enzyme-inducing drugs (e.g., carbamazepine, phenytoin, rifampicin, St. John's Wort), Pre-existing liver disease (controversial).

Diagnosis

Clinical assessment

Based on history of ingestion: Amount ingested (mg/kg or total grams) and time of ingestion are CRITICAL. Clinical features are unreliable indicators of toxicity in the early phase (first 24 hours). Assess risk factors.

Investigations

  • Serum Paracetamol Level: ESSENTIAL. Draw level at ≥4 hours post-ingestion (levels drawn earlier are unreliable for risk assessment). Plot the level against time since ingestion on the standard Rumack-Matthew treatment nomogram (use the 150 mcg/mL at 4h line, or local equivalent). This determines the risk of hepatotoxicity and the need for NAC treatment.
  • If time of ingestion is unknown, staggered, or presentation is late (>8-10 hours), obtain a paracetamol level and LFTs immediately. Treat with NAC if level is detectable or LFTs are abnormal, pending further assessment.
  • Liver Function Tests (LFTs): AST, ALT, Bilirubin, INR (or PT). Obtain baseline and monitor serially (daily) in patients requiring treatment or at risk. AST often rises first and peaks highest.
  • Renal Function Tests (Urea, Creatinine): Monitor for acute kidney injury.
  • Blood Glucose: Monitor for hypoglycemia, especially if liver failure develops.
  • Acid-Base Status (ABG or VBG): Check for metabolic acidosis in severe cases.
  • Pregnancy test in females of childbearing age (paracetamol crosses placenta, NAC is safe and indicated).

Diagnostic criteria

Need for treatment determined by: Paracetamol level plotting above the treatment line on the Rumack-Matthew nomogram (at ≥4 hours post-ingestion). OR History of ingesting a potentially toxic dose (>150 mg/kg or >7.5g) AND level is unavailable or delayed beyond 8 hours post-ingestion. OR Unknown time of ingestion or staggered overdose with detectable paracetamol level or evidence of liver injury (elevated AST/ALT). OR Any patient presenting with evidence of liver failure possibly related to paracetamol.

Management

Non-pharmacological management

  • Stabilization: ABCDE approach.
  • GI Decontamination: Activated charcoal (Oral/NGT, 50g adult, 1g/kg child) if patient presents within 1-2 hours of a potentially toxic ingestion. May reduce drug absorption but should NOT delay administration of NAC if indicated.
  • Gastric lavage: Generally not indicated unless massive ingestion presenting very early (<1 hour).
  • Supportive care: Antiemetics for nausea/vomiting. IV fluids for hydration. Monitor and manage complications (liver failure, renal failure, coagulopathy, hypoglycemia, encephalopathy) - usually requires hospital/intensive care setting.

Pharmacological treatment

  • ANTIDOTE: N-Acetylcysteine (NAC): CRITICAL treatment. Replenishes hepatic glutathione stores, detoxifies the toxic metabolite (NAPQI). Most effective if started within 8 hours of ingestion, but still provides benefit if started later (even >24 hours or with established liver injury).
  • IV NAC Regimen (UCG Recommended - 21-hour total infusion):
  • 1. Loading dose: 150 mg/kg in 200 mL Dextrose 5% infused over 60 minutes.
  • 2. Second infusion: 50 mg/kg in 500 mL Dextrose 5% infused over 4 hours.
  • 3. Third infusion: 100 mg/kg in 1000 mL Dextrose 5% infused over 16 hours.
  • (Maximum single dose caps mentioned in UCG: 15g, 5g, 10g respectively).
  • Oral NAC regimen: Alternative if IV unavailable (less common, requires longer course, vomiting problematic).
  • Adverse Reactions to IV NAC: Anaphylactoid reactions (non-IgE mediated histamine release - flushing, rash, urticaria, angioedema, bronchospasm, hypotension) are common, especially during loading dose. Usually mild-moderate. Management: Temporarily stop or slow infusion rate, administer antihistamines (e.g., chlorpheniramine), consider bronchodilators if needed. Restart infusion at slower rate once symptoms resolve. True anaphylaxis is rare.
  • Treatment of Complications (Hospital/RR): Vitamin K for coagulopathy (INR >1.5). Lactulose/Rifaximin for hepatic encephalopathy. Management of hypoglycemia. Renal replacement therapy (dialysis) for acute kidney injury. Liver transplantation consideration for fulminant hepatic failure (limited availability).

Monitoring

Monitor paracetamol level (initial risk assessment). Monitor LFTs (AST, ALT, Bilirubin, INR), renal function, glucose, acid-base status daily or more frequently if severe, until trend is improving and patient stable. Monitor vital signs. Monitor closely for adverse reactions during NAC infusion. Monitor neurological status for signs of encephalopathy.

Complications

  • Acute liver injury / Hepatotoxicity
  • Fulminant hepatic failure
  • Hepatic encephalopathy
  • Coagulopathy and bleeding
  • Acute kidney injury / Renal failure
  • Hypoglycemia
  • Metabolic acidosis (lactic acidosis)
  • Pancreatitis (less common)
  • Death

Prevention

  • Patient education on correct paracetamol dosage and maximum daily limits.
  • Awareness of paracetamol content in various combination cold/flu and pain relief products to avoid unintentional stacking.
  • Safe storage of medications, out of reach of children.
  • Using accurate measuring devices for liquid formulations in children.
  • Limiting pack sizes available for sale over-the-counter.
  • Mental health support for individuals at risk of intentional overdose.

Patient education

  • Explain the risk of liver damage from overdose.
  • Emphasize the importance of taking paracetamol only as directed and avoiding combination products without checking total dose.
  • Importance of seeking immediate medical attention after a suspected overdose, even if feeling well initially.
  • Explain the need for NAC treatment if indicated.
  • If overdose was intentional, stress the need for psychiatric evaluation and support.

Uganda-specific notes

Paracetamol is widely available and commonly used. Overdose is frequent. Accurate history (dose, time) is crucial but often difficult. Rely on the 4-hour paracetamol level and Rumack-Matthew nomogram for risk assessment when possible. Prompt administration of NAC within 8 hours is key for preventing liver damage. The UCG provides a clear IV NAC protocol. Be prepared to manage anaphylactoid reactions to NAC. Liver transplantation is generally not an option in Uganda, making early NAC treatment paramount.

References

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 1, Section 1.3.5

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