Toxic paracetamol

Paracetamol is widely available and has been around since the 1950s. It is widely prescribed and cheap to buy over-the-counter, making it a common drug taken in overdose. It is a very useful analgesic (alone or in combination) and also is an antipyretic. It is normally found as a 500 mg tablet, but it is often combined with other active ingredients in various preparations.

In the UK it is the most common agent of intentional self-harm and is responsible for approximately 70,000 cases per year.It is the most common cause of  acute liver failure.

• It is important to remember that, when used at therapeutic levels, paracetamol is safe and effective.
• Paracetamol overdose may occur intentionally and accidentally; the latter due to the high number of combination products available over-the-counter.

 Based on the dose of paracetamol ingested (mg/kg body weight):

• Less than 150 mg/kg - unlikely
• More than 250 mg/kg - likely
• More than 12 g total - potentially fatal

• Paracetamol can cause serious or fatal adverse effects at around 150 mg/kg for most adults.
• The level is higher for young children. NB: Toxbase® says there is no choice but to treat children younger than 6 years the same as adults. However, there is a large body of data in the published literature that shows the threshold for likely hepatotoxicity exceeds 225 mg/kg for this age group and so using a value of 200 mg/kg is a safe option and reduces waiting times and the number of unnecessary blood tests with their associated distress.
• There is a theoretical argument for increased risk with enzyme induction or low glutathione reserves. There are case reports of chronic alcoholics taking relatively small overdose (OD) or even therapeutic doses of paracetamol who develop liver failure. However close examination of these case reports shows up some inconsistencies and suggests that it is unclear that these all provide any substantial evidence supporting the hypothesis. Even the seminal paper that formed the basis of the UK guidelines suggests that there is no evidence base for the practice of a 50% high-risk line on the nomogram.