Paracetamol overdose: new guidance on the use of intravenous acetylcysteine

PLEASE NOTE: This guidance is being reviewed and may require updating. RCEM strongly recommend that you refer to Toxbase for the most up to date guidance.

The College Quality in Emergency Care Committee (QEC) has worked closely with the Medicines & Healthcare Products Regulatory Agency (MHRA) following a review by the Commission on Human Medicines of the treatment of paracetamol poisoning.  Professor Simon Thomas chaired the implementation group, with input from the National Poisons Information Service (NPIS).

The key changes from previous guidance are:  

• A single treatment line regardless of hepatotoxicity risk (see Annex I, below).
• The duration of administration of the first dose of intravenous acetylcysteine is increased from 15 minutes to 1 hour.
• Removal of hypersensitivity as a contraindication to treatment with acetylcysteine.
• Provision of weight-based dosing tables for adults and children.
• A Technical Information Leaflet (TIL) which gives more detailed instructions on the preparation of acetylcysteine infusions (see Annex II, below).

These changes are intended to simplify treatment decisions, minimise allergic reactions and reduce prescribing errors.  They reflect the findings of the Commission on Human Medicines that risk factor assessment was difficult and inconsistently applied in clinical practice. There have also been many reports of prescribing and administration errors.

This new guidance will be published in the next edition of the British National Formulary (BNF). We would therefore recommend that you introduce these changes as soon as possible, and cascade this information to all clinical staff in your Emergency Department. Full details regarding the CHM recommendations can be found on the MHRA website.

Download the summary of changes

Download Annex 1: the treatment nomogram and Annex 2: Technical Information Leaflet on Acetylcysteine injection information

You can also download examples of proformas for paracetamol poisoning (published here with thanks to Martin Wiese at Leicester Royal Infirmary)

Download paracetamol poisoning proforma to guide ED management of ORAL ingestions in adults (Leicester Royal Infirmary, Nov 2017)

Download paracetamol poisoning proforma to guide management of all ORAL ingestions in patients aged >1 month and <16 years old  (Leicester Royal Infirmary, Nov 2017)

Download proforma management of oral Paracetamol poisoning after 21-hour NAC treatment course
 
Annex 1: Revised paracetamol overdose treatment nomogram


 

Annex 2: ACETYLCYSTEINE 200mg/mL INJECTION FOR INFUSION

 ADMINISTRATION INFORMATION FOR THE HEALTHCARE PROFESSIONAL

Acetylcysteine should be administered by intravenous infusion preferably using Glucose 5% as the infusion fluid. Sodium Chloride 0.9% solution may be used if Glucose 5% is not suitable. The full course of treatment with acetylcysteine comprises of 3 consecutive intravenous infusions. Doses should be administered sequentially with no break between the infusions. The patient should receive a total dose of 300 mg/kg body weight over a 21 hour period.

Adults

• Weigh the patient to determine the correct weight band.
• Use the adult dosage table to determine the appropriate volume of acetylcysteine (ampoule volume) to be added to the infusion fluid for each of the 3 infusion periods.

First infusion
Add the appropriate volume of acetylcysteine injection to 200 mL of infusion fluid and infuse over 1 hour.

Second infusion
Add the appropriate volume of acetylcysteine injection to 500 mL of infusion fluid and infuse over the next 4 hours.

Third infusion
Add the appropriate volume of acetylcysteine injection to 1 litre of infusion fluid and infuse over the next 16 hours.

Adult Dosage Table

1 Dose calculations are based on the weight in the middle of each band. If the patient weighs less than 40kg use the paediatric dosage table.
2 Ampoule volume has been rounded up to the nearest whole number
Please Note: The Summary of Product Characteristics should be referred to for full prescribing information.  This version is provided by the MHRA and is subject to further user-testing.

Children

Children are treated with the same doses and regimen as adults. However, the quantity of intravenous fluid used has been modified to take into account age and weight, as fluid overload is a potential danger. Doses should be administered sequentially using an appropriate infusion pump.

• Preparation and administration of paediatric infusions
• Weigh the child to determine the correct weight band.
• Read off the table the total infusion volume required for each dose according to the weight of the child and make up the solutions according to the directions below.

First Infusion

• Prepare a 50 mg/mL solution by diluting each 10 mL ampoule of acetylcysteine (200 mg/mL) with 30 mL glucose 5% or sodium chloride 0.9% to give a total volume of 40 mL.
• Prepare the appropriate volume for the weight of the child.
• The dose is infused over 1 hour at the infusion rate stated in the table.

Second Infusion

• Prepare a 6.25 mg/mL solution by diluting each 10 mL ampoule of acetylcysteine (200 mg/mL) with 310 mL glucose 5% or sodium chloride 0.9% to give a total volume of 320 mL
• Prepare the appropriate volume for the weight of the child.
• The dose is infused over 4 hours at the infusion rate stated in the table.

Third Infusion

• Prepare a 6.25 mg/mL solution by diluting each 10 mL ampoule of acetylcysteine (200 mg/mL) with 310 mL glucose 5% or sodium chloride 0.9% to give a total volume of 320 mL.
• Prepare the appropriate volume for the weight of the child.
• The dose is infused over 16 hours at the infusion rate stated in the table.

For example for a child weighing 12 kg, the first infusion would be 38 mL infused at 38 mL/h over 1 hour,the second infusion would be 100 mL infused at 25 mL/h over 4 hours and the third infusion is 208 mL infused at 13 mL/h over 16 hours.

Pediatric Dosage Table