Treatment of Paracetamol Overdose

This guideline reflects the local NHSGGC policy on acetylcysteine use in adult paracetamol overdoses and is based on the Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning (SNAP) regime. The same dose of N-acetylcysteine is administered in this regime but over a 12-hour (not 21-hour) treatment period. While the MHRA has not yet approved its use, TOXBASE now lists the regime as a recognised treatment period. 

TOXBASE (password required) should continue to be used as a clinical decision support resource in conjunction with the National Poisons Information Service (NPIS, 0344 892 0111).

Introduction

In overdose the potential risk of a patient having significant liver damage is directly proportional to the amount of paracetamol ingested. Acetylcysteine IV (N-acetylcysteine, Parvolex^®, NAC) is the treatment of choice. It has near 100% efficacy in preventing paracetamol-induced hepatotoxicity if given within the first 8 hours from ingestion of overdose. It may also be effective up to and possibly beyond 24 hours. 

Management of a patient suffering from a paracetamol overdose is dependent on the presentation scenario and time from ingestion. In some scenarios the paracetamol level can be plotted against a single treatment line on the paracetamol treatment nomogram. The standard local protocol is acetylcysteine IV in two infusions with the option to extending depending on biochemical criteria.

Management protocols

Patient should undergo a further hospital medical assessment if:

• Self-harm - all patients (irrespective of reported ingested dose or timing, clinical judgement required if historical).
• Therapeutic excess (any of the following):
  • All symptomatic patients
  • Patients who have ingested (any of the following):
    • ≥75mg/kg of paracetamol over a period of <1hour 
    • ≥75mg/kg in any 24-hour period and who have ingested more than the licensed dose in any 24-hour period.
    • more than the licensed daily dose in any 24-hour period and taken any paracetamol products in the preceding 2 or more days. 

If not proceeding to further hospital medical assessment, there needs to be a high degree of certainty regarding the clinical scenario. Clinical judgement is required in respect to the therapeutic excess group.

Complex cases should be discussed with toxicology on call (NPIS) via switchboard. Patients with paracetamol levels twice the nomogram or over 300mg/L should also be considered for discussion.

Follow the initial management outlined below for:

• Paracetamol overdose presenting 0-8 hours (ingested total overdose in ≤1 hour time period)
• Paracetamol overdose presenting 8-24 hours (ingested total overdose in ≤1 hour time period)
• Paracetamol overdose presenting >24 hours (ingested total overdose in ≤1 hour time period)
• Staggered overdoses (ingested total overdose in >1 hour time period in the context of self-harm)
• Therapeutic excess paracetamol overdose (ingested total overdose in >1 hour time period no self-harm intent)

Use the NHSGGC Acetylcysteine Prescribing and Administration Chart which is located in all Emergency Departments and Medical Receiving areas.

Special groups

• Low weight - patients <30kg, use the paediatric regime on TOXBASE (password required) for management as this protocol is not applicable.
• High weight - patients >110kg can be treated using this protocol. For this group a weight of 110kg should be used to calculate their toxic dose (mg/kg) and their drug dose.
• Pregnancy - patients who are pregnant can be treated using this protocol. Their toxic dose (mg/kg) should be calculated using their booking or pre-pregnancy weight. The drug dose should be calculated using their current weight.
• Paediatric - this protocol does not apply to patients <16years old. See TOXBASE (password required) for paediatric dosing table.
• Overdose from IV paracetamol - this protocol does not apply, seek advice from NPIS (0344 892 0111). 
• Patients when IV acetylcysteine treatment is not possible - seek advice from NPIS (0344 892 0111).

Paracetamol overdose treatment nomogram

• Graph Paracetamol Overdose Nomogram

  Crown copyright material is reproduced by permission of the Medicines and Healthcare Products Regulatory Agency under delegated authority from the Controller of HMSO.

• Determine the need for acetylcysteine by plotting the measured plasma paracetamol level (in mg/L) against the time since ingestion. If plasma level falls above the line then give acetylcysteine as per the management protocols above.
• If timing of ingestion is unreliable then consider treating with acetylcysteine regardless of whether the plasma level is above or below the treatment line.
• Likewise if ALT / INR is newly abnormal, consider treating with acetylcysteine even if the paracetamol level is below the treatment line.
• The nomogram becomes less reliable after 15 hours. 
• If overdose is staggered (ingested over >1 hour) then the nomogram is unreliable; see management protocols above.

N.B. In NHSGGC paracetamol plasma levels reported in units of mg/L (use the left Y axis).

Hypersensitivity and anaphylaxis reaction

• Hypersensitivity and anaphylaxis reactions with acetylcysteine are not contraindications as the benefit of treatment still outweighs the risk of not treating. True anaphylaxis is rare with acetylcysteine.
• Hypersensitivity reactions are directly proportional to the serum acetylcysteine level and most common during the 1st infusion. If a reaction occurs then pause the infusion for 30 minutes and give symptomatic treatment as below:
  • Bronchospasm - nebulised bronchodilators
  • Nausea - IV / oral anti-emetic (be mindful of QTc interval if polydrug overdose)
  • Flushing / itch - IV antihistamine
  • True anaphylaxis - see guideline

Acute Mental Health Liaison referral

All adult patients (>18 years old) who attend hospital following (or threatening) an episode of self-harm should be reviewed by psychiatry liaison prior to discharge. See NHSGGC StaffNet / Partnerships / MHP/ Specialist services / Acute Mental Health Liaison Service (link only active when linked in to NHSGGC network) for the referral process and contact details. 

Guideline reviewed: February 2023

Page last updated: March 2023