Clinical Practice Guidelines

Paracetamol poisoning

  • See also:  General Management of Acute Poisoning Guideline

    Background

    Paracetamol is the most widely used over-the-counter analgesic agent in the world. It is involved in a large proportion of accidental paediatric exposures and deliberate self-poisoning cases and is the leading pharmaceutical agent responsible for calls to poisons information centres in Australia and New Zealand. Paracetamol is also the single most commonly taken drug in overdoses that lead to hospital presentation and admission. Hepatic failure and death are uncommon outcomes, although paracetamol remains the most important single cause of acute fulminant hepatic failure in Western countries

    How to assess

    Patients requiring management

    • Acute ingestion of > 200mg/kg
    • Ingestion of unknown quantity
    • Repeated supratherapeutic ingestion of > 100mg/kg/day

    Consider the possibility of co ingestions, either accidental or deliberate

    Acute management

    • Serum paracetamol concentration at (or as soon as possible after) 4 hours post ingestion determines the need for N-acetyl cysteine (NAC) administration.  (see nomogram)
    • There is no benefit in measuring paracetamol concentration earlier than 4 hours post ingestion.
    • It is safe to wait for the paracetamol concentration to decide on the need for NAC in all cases that present within 8 hours of ingestion AND where a paracetamol concentration result will be available for interpretation within 8 hours of ingestion.
    • Patients who present > 8 hours after a toxic ingestion (>200 mg/kg) or after an ingestion in association with symptoms of toxicity (RUQ pain or tenderness, nausea, vomiting) should be commenced on NAC immediately.  The decision to continue or cease NAC is then based on the paracetamol concentration. 
    • Delaying NAC administration beyond 8 hours post ingestion is associated with a progressive increased risk of liver injury.
    • There is little evidence to guide management in repeated supratherapeutic doses.  Potential toxicity should be assessed when:
      • > 200 mg/kg (or 10g) ingested over a 24 hour period
      • > 150 mg/kg/day (or 6 g) ingested over a 48 hour period
      • > 100 mg/kg/day ingested over a 72 hour period
    • See management algorithm and NAC infusion guide.

    Paracetamol ingestion flowchart

    paracetamol_single_OD

    Nomogram for acute single dose paracetamol poisoning

    paracetamol_multiple_OD

    Sustained release paracetamol

    NAC should be commenced in any patient who reports ingestion of 200 mg/kg or 10g of sustained release paracetamol.

    An initial paracetamol concentration should be measured 4 hours post ingestion or immediately if presentation is >4 hours after ingestion. If this concentration is above the treatment line then the full 21 hour infusion of NAC is required.

    If the initial paracetamol concentration is below the line then NAC should be continued and another paracetamol concentration obtained 4 hours after the initial concentration. NAC can be discontinued if both paracetamol concentrations are below the treatment line.

    Sustained release paracetamol flow chart

    N-Acetyl cysteine (NAC) infusion instructions

    The standard administration of NAC is a 3 stage infusion giving a total dose of 300 mg/kg:

    1. 150 mg/kg over the first hour
    2. 50 mg/kg over the next 4 hours
    3. 100mg/kg over the next 16 hours

    For patients >110 kg, calculate the dose based on 110 kg body weight.

    NAC may be diluted in 5% dextrose or 0.9% saline (normal saline).  It can also be diluted in combination dextrose-saline solutions not exceeding these concentrations including 0.45% saline in 5% dextrose, and 0.9% saline in 5% dextrose.

    The volume and choice of fluid for each stage of the infusion needs to be appropriate for the age and weight of the child and clinical circumstances.  In the adolescent patient, it is generally appropriate to follow the standard published recommendations for NAC administration and use convenient volumes for administration:

    For adolescent/adult:

    • 150 mg/kg in 250 or 500 ml over 1 hour
    • 50 mg/kg in 500 ml over 4 hours
    • 100 mg/kg in 1000 ml over 16 hours

    However, this results in a total of 1700mls of 5% dextrose which is inappropriate for smaller children.

    For smaller children a suggested approach is:

    NAC Dose Dilute in (saline or dextrose) Duration (Rate)
    150 mg/kg 250 ml bag 1 hour (250 ml/hr)
    50 mg/kg 250 ml bag 4 hours (65 ml/hr)
    100mg/kg 250 ml bag 16 hours (15 ml/hr)

    For infants, even smaller volumes may be required.  Doses can be diluted in 100 ml bags if available or added to an appropriate volume in a burette.

    In all cases, additional maintenance fluids can be given if required, or NAC may be administered in larger volume bags if more convenient.

    Note: Monash Health uses a different NAC infusion protocol to the one contained in this guideline. Information is available via PROMPT, or by discussing with the Monash on call toxicologist.

    Additional notes:

    Anaphylactoid reactions to NAC may occur (wheeze, rash).  In these cases, cease the infusion for 30 minutes, give promethazine then recommence the infusion at half the previous rate.  Slowly increase the rate until the desired rate is again reached.

    When to admit/consult local paediatric team, or who/when to phone consult at RCH:

    Patients requiring NAC infusion.

    When to consider transfer:

    Patients requiring care beyond the comfort level of the hospital

    Link to NETS/PETS phone number

    Discharge requirements:  

    • In those patients requiring treatment with NAC, an ALT, renal function (5% of patients with significant paracetamol toxicity will development acute renal injury) and paracetamol concentration should be measured at the completion of the 21 hour infusion.
    • If the ALT or renal function is elevated or the paracetamol concentration is > 120 micromol/L continue the NAC infusion at the current rate and seek specialist advice.