Paracetamol overdose in adults

Toxic dose

A toxic dose is considered as >75mg/kg within a 24-hour period.[3]National Poisons Information Service. TOXBASE. Paracetamol. 2023 [internet publication]. https://www.toxbase.org

Acute toxic overdose

Acute toxic overdose is defined as an ingestion of >75 mg/kg of paracetamol within a 1-hour period.[3]National Poisons Information Service. TOXBASE. Paracetamol. 2023 [internet publication]. https://www.toxbase.org

Serum paracetamol concentration

For acute paracetamol oral overdose, specific management is dependent on the serum paracetamol concentration relative to the time of ingestion. A timed serum paracetamol concentration is drawn at least 4 hours after ingestion to risk-stratify likelihood of liver injury and the need for acetylcysteine treatment.[47]Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975 Jun;55(6):871-6. http://www.ncbi.nlm.nih.gov/pubmed/1134886?tool=bestpractice.com Patients who present within 4 hours following ingestion should have a serum paracetamol concentration checked at 4 hours. The serum concentration is plotted on a treatment nomogram to determine whether treatment with antidote (acetylcysteine) is required.

In the UK, levels are plotted on a graph showing serum paracetamol concentration versus time from ingestion that has a single line joining 100 mg/L at 4 hours with 15 mg/L at 15 hours. Acetylcysteine treatment is started if the paracetamol level falls on or above this line. MHRA: paracetamol treatment graph Opens in new window

In Australia and New Zealand, a guideline has been devised for initiating acetylcysteine treatment similar to the Rumack-Matthew nomogram used in US.[48]Chiew AL, Reith D, Pomerleau A, et al. Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. Med J Aust. 2020 Mar;212(4):175-83. http://www.ncbi.nlm.nih.gov/pubmed/31786822?tool=bestpractice.com ​​

In repeated supratherapeutic ingestion and staggered overdoses, the serum paracetamol concentration may be low or undetectable, and is not used to determine initial treatment, but is used for monitoring. Serum paracetamol concentration levels cannot be used for the management of intravenous overdose of paracetamol. It is recommended that the advice of a medical toxicologist is sought regarding the management of intravenous overdose of paracetamol.

Hepatotoxicity

Serious hepatotoxicity after paracetamol overdose is a serum aspartate aminotransferase (AST) concentration >1000 IU/L.[1]Ferner RE, Dear JW, Bateman DN. Management of paracetamol poisoning. BMJ. 2011 Apr 19;342:d2218. http://www.ncbi.nlm.nih.gov/pubmed/21508044?tool=bestpractice.com

Hepatic encephalopathy: West Haven classification system[35]Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002 Mar;35(3):716-21. http://www.ncbi.nlm.nih.gov/pubmed/11870389?tool=bestpractice.com

• Grade 4: coma, with or without response to painful stimuli.

• Grade 3: drowsy but rousable, unable to perform mental tasks, disorientation to time and place, marked confusion, amnesia, occasional fits of rage, speech present but incomprehensible.

• Grade 2: drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behaviour, intermittent disorientation. Asterixis is obvious.

• Grade 1: mild confusion, euphoria, or depression, decreased attention, slowing of ability to perform mental tasks, irritability, disorder of sleep pattern such as inverted sleep cycle. Asterixis can be detected.

• Grade 0: subclinical; normal mental status but minimal changes in memory, concentration, intellectual function, coordination.