Overdose may occur after an acute single ingestion of a large amount of paracetamol or paracetamol-containing medication, or repeated ingestion of an amount exceeding recommended dosage.
Patients are often asymptomatic or have only mild gastrointestinal symptoms at initial presentation. Untreated paracetamol poisoning may cause varying degrees of liver injury over the 2 to 4 days following ingestion, including fulminant hepatic failure.
Rarely, massive overdose may initially present with coma and severe metabolic acidosis. Presentation with coma may also occur if a combination preparation of paracetamol and opioid is taken in overdose, or after an overdose of multiple drugs.
Hepatotoxicity is extremely rare in patients treated with acetylcysteine within 8 hours of an acute paracetamol overdose. The efficacy of acetylcysteine decreases subsequent to the first 8 hours following an acute paracetamol overdose, with a corresponding stepwise increase in hepatotoxicity with increasing treatment delays between 8 and 16 hours.
The recommended dose of paracetamol is 4 g (or 75 mg/kg) in 24 hours for an adult patient. Any ingestion exceeding this is regarded as an overdose. However, toxicity is extremely unlikely if <75 mg/kg paracetamol has been ingested within a 24-hour period. Single acute overdose is defined as an ingestion of >4 g (or >75 mg/kg) in a period of <1 hour.
A staggered overdose is the ingestion of multiple doses of paracetamol over a period of >1 hour. The Commission on Human Medicines (CHM) no longer defines a staggered overdose in terms of mg/kg/day.
A repeated supratherapeutic overdose is defined as more than one ingestion of paracetamol to a total of >75 mg/kg within a 24-hour period.
The National Poisons Information Service in the UK recommends that, for the purposes of calculating potentially toxic doses, the following be considered:
1. For pregnant patients, the toxic dose is calculated using the patient's pre-pregnancy weight.
2. For patients weighing >110 kg, the toxic dose should be calculated using a maximum of 110 kg instead of the patient's actual weight.
The definition of hepatotoxicity after paracetamol overdose is a serum AST concentration at least 1000 IU/L.
Associate Professor of Emergency Medicine
University of Colorado School of Medicine
The employer of KH received research grants from McNeil Consumer Healthcare, a manufacturer of acetaminophen.
Staff Specialist in Emergency Medicine
The Prince Charles Hospital
AN declares that he has no competing interests.
Professor Kennon Heard and Dr Alastair Newton would like to gratefully acknowledge Professor Allan R. Mottram, a previous contributor to this topic.
ARM declares that he has no competing interests.
Department of Toxicology
Rocky Mountain Poison & Drug Center
SP declares that he has no competing interests.
Division of Research
Department of Emergency Medicine
Albert Einstein Medical Center
GFOM declares that he has no competing interests.
Department of Medicine
Emergency Physician and Medical Toxicologist
McGill University Health Centre
Centre Antipoison du Québec
SG declares that she is an unpaid co-investigator in the Canadian Acetaminophen Overdose Study and unpaid co-chair of the Extracorporeal Treatment In Poisoning workgroup.
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