Paracetamol overdose
Key messageThe key message for mental health services is treat ALL reported paracetamol overdoses as a potential emergency. All actual or suspected paracetamol overdoses should be referred to hospital (Accident & Emergency) for assessment, including blood tests.
Due to the ease of access paracetamol is frequently used in overdose in self-harm attempts. Paracetamol is both acutely and accumulatively toxic. Toxic doses of paracetamol may cause severe hepatocellular necrosis which may ultimately be fatal. Liver damage is maximal 3 – 4 days after paracetamol overdose. Therefore, even if there are no significant early symptoms, patients who report taking a paracetamol overdose should be transferred to an acute hospital urgently.
For CPNsWhen a CPN takes someone with a suspected overdose of paracetamol to the emergency department they should have a handover discussion with the receiving service, indicating what the follow up management should be if the person is deemed medically fit, including psychiatric hospital admission.
ToxbaseThe following advice is taken from the TOXBASE entry for paracetamol:
Management: Management of paracetamol overdose depends on the type of overdose involved. The NPIS has defined different types of paracetamol overdose as follows:

• Paracetamol overdose over a period of one hour or less: Excessive amounts of paracetamol are ingested over a period of less than one hour, usually in the context of self-harm.
• Staggered paracetamol overdose (non-therapeutic ingestions of excessive paracetamol over a period of more than one hour): Excessive amounts of paracetamol are ingested over longer than one hour, usually in the context of self-harm.
• Therapeutic excess (ingestions of excessive paracetamol with intent to treat pain or fever and without self-harm intent): Therapeutic paracetamol excess, where patients ingest paracetamol at a dose greater than the licensed daily dose AND more than or equal to 75 mg/kg/24hrs, for the treatment of pain or fever without self-harm intent is common. This usually occurs over more than 24 hours, but may occur over less than 24 hours. Therapeutic excess can involve use of excessive doses of the same paracetamol product or inadvertent use of more than one paracetamol-containing product at the same time.

All patients who meet any of the following criteria should be referred to hospital for medical
assessment:

• Patients who have ingested paracetamol in the context of self-harm (irrespective of
  reported dose)
• Symptomatic patients
• Patients who have ingested 75 mg/kg* or more paracetamol over a period of one hour or
  less
• Patients where the time of ingestion is uncertain but the dose ingested is 75 mg/kg* or more

*For a 60kg individual 75mg/kg equates to 9 tablets.
MHRA advice is that treatment with acetylcysteine should be commenced without delay in ALL patients who have ingested a staggered overdose.

Paracetamol overdose: management
The following is based on 2012 Commission on Human Medicines (CHM) review of paracetamol overdose management. The big change in these guidelines was the removal of the 'high-risk' treatment line on the normogram. All patients are therefore treated the same regardless of risk factors for hepatotoxicity. The National Poisons Information Service/TOXBASE should always be consulted for situations outside of the normal parameters.

The minority of patients who present within 1 hour may benefit from activated charcoal to reduce absorption of the drug.

Acetylcysteine should be given if:

• the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity
• there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or
• patients who present 8-24 hours after ingestion of an acute overdose of more than 150 mg/kg of paracetamol even if the plasma-paracetamol concentration is not yet available
• patients who present > 24 hours if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal
  • acetylcysteine should be continued if the paracetamol concentration or ALT remains elevated whilst seeking specialist advice

Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.



King's College Hospital criteria for liver transplantation (paracetamol liver failure)
Arterial pH < 7.3, 24 hours after ingestion

or all of the following:

• prothrombin time > 100 seconds
• creatinine > 300 µmol/l
• grade III or IV encephalopathy

*an overdose is considered staggered if all the tablets were not taken within 1 hour


Paracetamol overdose: risk factors
The following groups of patients are at an increased risk of developing hepatotoxicity following a paracetamol overdose:

• patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John's Wort)
• malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days

Interestingly, acute alcohol intake, as opposed to chronic alcohol excess, is not associated with an increased risk of developing hepatotoxicity and may actually be protective.