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Liver damage is possible in adults who have taken 10 g or more of Paracetamol. Ingestion of 5g or more of Paracetamol may lead to liver damage if the patient has risk factors.
Risk Factors: If the patient: Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John's Wort or other drugs that induce liver enzymes; or; b. Regularly consumes ethanol in excess of recommended amounts; or; c. Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms: Toxic symptoms include vomiting, abdominal pain, hypotension, sweating, pallor, nausea, anorexia and abdominal pain. The most serious adverse effect of acute overdose of paracetamol is a dose-dependent, potentially fatal hepatic necrosis. Clinical and laboratory evidence of hepatoxicity may be delayed for up to one week. Major manifestations of liver failure such as jaundice, hypoglycaemia and metabolic acidosis may take at least 3 days to develop. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Treatment: In cases of overdose, methods of reducing the absorption of ingested drug are important. Despite lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Gastric lavage is essential even if several hours have elapsed. Prompt administration of 50g activated charcoal and 500ml iced mannitol 20% by mouth, may reduce absorption. Plasma paracetamol concentration should be measure at 4 hours or later after ingestion (earlier concentration is unreliable). If the history suggests that 15g Paracetamol or more has been ingested, administer one of the following antidotes: Acetylcysteine 20% I.V.: Administer intravenously, 20% acetylcysteine immediately without waiting for positive urine test or plasma level results: initial dose of 150mg/kg over 15 minutes, followed by continuous infusion of 50mg/kg in 500ml 5% glucose/dextrose over 4 hours and 100mg/kg in 1L 5% glucose/dextrose over 16 hours. OR; Oral Methionine: 2.5g immediately followed by three further doses of 2.5g at four hourly intervals. For a 3 years old child, 1g methionine every four hours for four doses has been used; OR; Oral Acetylcysteine 5%: 140mg/kg as a loading dose, then 70mg/kg every 4 hours for a total of 17 maintenance doses. If more than ten hours have elapsed since the overdosage was taken, the antidote may be in ineffective.
