ACETAMINOPHEN (PARACETAMOL) POISONING

ACETAMINOPHEN (PARACETAMOL) POISONING

Overdosage of acetaminophen is the most common pediatric poisoning and can produce severe hepatotoxicity. The incidence of hepatotoxicity in adults and adolescents has been reported to be 10 times higher than in children younger than age 5 years. In the latter group, fewer than 0.1% develop hepatotoxicity after acetaminophen overdose. In children, toxicity most commonly results from repeated overdosage arising from confusion about the age-appropriate dose, use of multiple products that contain acetaminophen, or use of adult suppositories.

Acetaminophen is normally metabolized in the liver. A small percentage of the drug goes through a pathway leading to a toxic metabolite. Normally, this electrophilic reactant is removed harmlessly by conjugation with glutathione. In overdosage, the supply of glutathione becomes exhausted, and the metabolite may bind covalently to components of liver cells to produce necrosis. Some authors have proposed that therapeutic doses of acetaminophen may be toxic to children with depleted glutathione stores. However, there is no evidence that administration of therapeutic doses can cause toxicity, and only a few inadequate case reports have been made in this regard.

Treatment

Treatment is to administer acetylcysteine. It may be administered either orally or intravenously. Consultation on difficult cases may be obtained from your regional poison control center or the Rocky Mountain Poison and Drug Center. Blood levels should be obtained 4 hours after ingestion or as soon as possible.

The nomogram is used only for acute ingestion, not repeated supratherapeutic ingestions. If the patient has ingested acetaminophen in a liquid preparation, blood levels obtained 2 hours after ingestion will accurately reflect the toxicity to be expected relative to the standard nomogram. Acetylcysteine is administered to patients whose acetaminophen levels plot in the toxic range on the nomogram. Acetylcysteine is effective even when given more than 24 hours after ingestion, although it is most effective when given within 8 hours

The oral (PO) dose of acetylcysteine is 140 mg/kg, diluted to a 5% solution in sweet fruit juice or carbonated soft drink. The primary problems associated with administration are nausea and vomiting. After this loading dose, 70 mg/kg should be administered orally every 4 hours for 72 hours.

For children weighing 40 kg or more, IV acetylcysteine (Acetadote) should be administered as a loading dose of 150 mg/kg administered over 15–60 minutes; followed by a second infusion of 50 mg/kg over 4 hours, and then a third infusion of 100 mg/kg over 16 hours.

For patients weighing less than 40 kg, IV acetylcysteine must have less dilution to avoid hyponatremia.

☆Aspartate aminotransferase (AST–SGOT), alanine aminotransferase (ALT–SGPT), serum bilirubin, and plasma prothrombin time should be followed daily. Significant abnormalities of liver function may not peak until 72–96 hours after ingestion.

☆Repeated miscalculated overdoses given by parents to treat fever are the major source of toxicity in children younger than age 10 years, and parents are often unaware of the significance of symptoms of toxicity, thus delaying its prompt recognition and therapy.