Paracetamol poisoning


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    This guideline has been adapted for statewide use with the support of the Victorian Paediatric Clinical Network

  • See also:

    Poisoning – acute guidelines for initial management
    Resuscitation

    Key points

    1. Suspect paracetamol poisoning in all adolescent deliberate self-poisonings.
    2. N-acetylcystine (NAC) is a safe and effective antidote. Time to NAC is crucial to protect the liver from significant toxicity.
    3. Stated timing and dose are often unreliable and this needs to be taken into consideration.
    4. Complicated overdose, including of a longer-acting form of paracetamol (e.g., Panadol osteo) and staggered ingestions should be discussed with a toxicologist.

    For 24 hour advice, contact Victorian Poisons Information Centre 131126

    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-poisonings. It is the leading pharmaceutical agent responsible for calls to poisons information centres in Australia and New Zealand. Hepatic failure and death are uncommon outcomes, although paracetamol remains the most important single cause of acute fulminant hepatic failure in Western countries.

    Patients requiring assessment

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

    Risk Assessment

    History:
    Dose:

    Stated or likely dose taken  
    Presented as syrup, immediate or modified- release tablets
    If possible determine the exact name and tablet size.
    Calculate the maximum possible dose per kg 

    Consider the possibility of co ingestions, either accidental or deliberate

    Clinical Signs & Symptoms
    Most patients who present within 24 hours of ingestion are asymptomatic.

    • Occasionally they complain of nausea, vomiting, pallor and diaphoresis.

    Right upper quadrant tenderness may begin to develop after this time.

    In untreated or undertreated cases, signs of hepatotoxicity and hepatic failure usually take 48 to 72 hours to develop, and may include hypotension and encephalopathy.

    • Signs of fulminant hepatic failure and coagulopathy may occur even later than this.

    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.
    • Children 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 and a toxicologist consulted 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
    • Consult Toxicologist in very large or massive dose ingestion (>30g) or if initial paracetamol concentration very high (ie ≥ double the nomogram value).
    • For IV paracetamol medication errors consult a toxicologist.
    • See management algorithm and NAC infusion guide. 

    Paracetamol ingestion flowchart


    Nomogram for acute single dose paracetamol poisoning



    Sustained Release Paracetamol

    NAC should be commenced in any child 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 in the nomogram then the full 20 hour infusion of NAC is required.

    If the initial paracetamol concentration is below the line in the nomogram 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 and are declining.


    N-Acetyl cysteine (NAC) infusion instructions
    The standard administration of NAC is a 2 stage infusion (recently changed from 3 stage infusion) giving a total dose of 300 mg/kg:

    1. 200 mg/kg over 4 hours
    2. 100 mg/kg over the next 16 hours

    DOSE Calculated based on actual body weight. For children >110 kg, calculate the dose based on 110 kg body weight.

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

    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 child, it is generally appropriate to follow the standard published recommendations for NAC administration.

    The volume of NAC needs to be included in the TOTAL volume of the infusion to avoid under-dosing (volumes specified in tables below are TOTAL volumes – ie. NAC volume plus fluid volume combined).


    For children >20 kg body weight:


    NAC Dose

    Dilute to
    (using sodium chloride or glucose)

    Rate and Duration  

    200 mg/kg

    TOTAL volume 250 mL

     62.5 mL/hr for 4 hours
    Infuse entire bag

    100 mg/kg

    TOTAL volume 500 mL

     31.25 mL /hr  for 16 hours
    Infuse the entire bag

    NOTE: this results in a total of 750 mL of fluid which is inappropriate for smaller children. 


    For children ≤20 kg body weight:


    NAC Dose

    Dilute to
    (using sodium chloride or glucose)

    Rate and Duration 

    200 mg/kg

    TOTAL volume 250 mL**

    62.5 mL/hr** for 4 hours
    Infuse entire bag

    100 mg/kg

    TOTAL volume 250 mL**

     15 ml/hr** for 16 hours
    Infuse entire bag

     

     

     

    **For infants, even smaller volumes may be required.  Doses can be diluted in 100 ml bags if available (note: the entire dose must be administered over the specified time.). For infants who are fluid restricted with concerns about fluid overload and a smaller total volume is required, contact hospital pharmacist for advice.


    Infant example


    NAC Dose

    Dilute to
    (using sodium chloride or glucose)

    Rate and Duration 

    200 mg/kg

    TOTAL volume 100 mL

     25 mL/hr for 4 hours
    Infuse entire bag

    100 mg/kg

    TOTAL volume 250 mL

    15.7 mL/hr for 16 hours
    Infuse entire bag

    Additional Fluids

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

    Monitoring

    At 18 hours into the NAC infusion (2 hours before completion), send bloods for

    • Paracetamol level
    • ALT
    • Urea, electrolytes, creatinine (5% of patients with paracetamol toxicity will develop acute renal injury)

    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.

     

    Dosing Errors

    NAC dosing or administration errors should be discussed with a toxicologist.


    Consider consultation with local paediatric team when:

    Admission should be considered for all children and young people with an intentional overdose.

    Consult Contact Victorian Poisons Information Centre 131126 for advice


    Consider transfer when:

    Children requiring care beyond the comfort level of the hospital

    For emergency advice and paediatric or neonatal ICU transfers, call the Paediatric Infant Perinatal Emergency Retrieval (PIPER) Service: 1300 137 650.


    Consider discharge when:

    No further NAC requirement and investigations are within normal limits (See Monitoring above)

    For deliberate ingestion a risk assessment should indicate that the patient is at low risk of further self harm in the discharge setting.

    Discharge information and follow-up:

    Poisoning prevention for children Parent information

    Victorian Poisons Information Centre: 13 11 26 www.austin.org.au/poisons

    Intentional self –harm: Referral to local mental health services eg Orygen Youth Health: 1800 888 320 

    Recreational poisoning: Referral to YoDAA, Victoria's Youth Drug and Alcohol Advice service: 1800 458 685.


    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 to the full rate over 30 minutes.

    Last updated February, 2018