Acetaminophen (Paracetamol) Poisoning

Descriptive text is not available for this imageBASICS

DESCRIPTION

  • Acetaminophen poisoning is one of the most common pediatric poisonings and may occur after an acute or chronic overdose.
  • Acetaminophen is the most popular pediatric analgesic/antipyretic, is sold under many brand names, and is often an ingredient in combination analgesic preparations.
  • Signs and symptoms of acetaminophen poisoning may initially be clinically occult or nonspecific and develop in stages if not properly treated:
    • <24 hours: nausea and vomiting, diaphoresis, and pallor
    • 24 to 72 hours (latent period): minimal symptoms, elevation of liver enzymes, right upper quadrant (RUQ) tenderness, jaundice
    • 72 to 96 hours: liver necrosis leading to signs and symptoms of liver failure, coagulation defects as well as renal damage and kidney failure, coma, and death
  • After acute overdose, a serum acetaminophen level above the treatment line of the Rumack-Matthew acetaminophen poisoning nomogram should be considered possibly hepatotoxic.
  • Serious hepatotoxicity after a single acute exploratory ingestion by young children is rare compared with that from intentional overdose by adolescents.
  • Many toddlers suffer hepatotoxicity from repeated supratherapeutic dosing of acetaminophen.

EPIDEMIOLOGY

  • Analgesics are the most common drugs implicated in poisoning exposures (11.2%) reported to United States poison control centers and account for 29% of all poisoning deaths in children <5 years old.
  • Acetaminophen preparations make up ~45% of all analgesic poisoning exposures reported to poison control centers.
  • In the United States, acetaminophen toxicity is responsible for >56,000 emergency room visits and about 500 deaths per year; 50% of these are reported as unintentional ingestions.
  • Acetaminophen poisoning is the most common cause of acute liver failure and liver transplantation in the United States.

ETIOLOGY

  • Single acute overdose of >200 mg/kg or 10 g
  • Repeated overdose of >150 mg/kg/24 h or 6 g/24 h for >2 days (or >100 mg/kg/24 h or 4 g/24 h if “susceptible”)

RISK FACTORS

  • Young age
  • Mental health disorders
  • Chronic pain syndromes
  • Glutathione depletion: prolonged vomiting, alcoholism, etc.
  • CYP2E1 induction (e.g., alcoholism, isoniazid therapy)

GENERAL PREVENTION

  • Acetaminophen should be stored with child-resistant caps, out of sight and reach of young children.
  • Appropriate dosing and correct use of acetaminophen products should be taught to patients with pain or fever.
  • Maximum daily dose should be included on packaging and discussed with patients and families.

PATHOPHYSIOLOGY

  • Rapid absorption occurs within 30 minutes to 2 hours with peak levels reached at 4 hours.
  • Acetaminophen is metabolized by the liver.
  • Most are metabolized through formation of hepatic glucuronide and sulfate conjugates and excreted in the urine.
  • Some are metabolized by the CYP450 mixed-function oxidase system, leading to the formation of the toxic N-acetyl-p-benzoquinone imine (NAPQI).
  • NAPQI is quickly detoxified by the glutathione under usual circumstances.
  • After overdose, metabolic detoxification can become saturated:
    • Drug elimination half-life becomes prolonged.
    • More NAPQI is produced.
    • Glutathione supply cannot meet detoxification demand.
    • Hepatic or renal toxicity may ensue.
  • Metabolization and elimination of acetaminophen takes approximately 2 hours; however, in patients with baseline hepatic dysfunction, it may take up to 17 hours.

COMMONLY ASSOCIATED CONDITIONS

  • Acetaminophen is often marketed in combination with other pharmaceuticals, which may complicate a drug overdose situation.
  • Intentional ingestions in adolescents frequently include coingestions with other substances (additional drugs, alcohol, etc.)

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