Starship Children’s Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.
PARACETAMOL POISONING
• Background
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•
Initial Management
Nomogram
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•
•
N-acetylcysteine (NAC)
Risk factors for paracetamol toxicity
References
Background
Paracetamol is the most common single agent involved in poisonous ingestions in young children.
While there is potential for serious liver damage if a large dose is ingested, in practice it is
extremely rare for a child to achieve toxic blood levels by ingesting paracetamol elixir (syrup).
Paracetamol is also commonly involved (often mixed with other drugs) in episodes of intentional
self harm by teenagers. In this situation, relatively large amounts of paracetamol may have been
ingested and this may not be disclosed in the history.
It is much more likely that a toxic level will be achieved under these circumstances.
Initial Management
Gastric Decontamination:
This has NO role in paracetamol elixir ingestions. Most of the drug is absorbed within 15 minutes
of elixir ingestion and it is very unlikely that a child will receive any intervention within this time
frame.
After a paracetamol tablet/capsule ingestion, then activated charcoal (1g/kg stat po) should be
considered if the dose ingested is > 200mg/kg AND the child presents within one hour of the
ingestion.
If the child will not drink the charcoal the NG route should only be used if the airway is protected.
This is because the risk of aspiration outweighs the small advantage of charcoal administration.
Drug Levels:
An accurate history of - the maximum possible dose, - the time, - possible other drugs ingested is
critical to management decisions.
Maximum possible dose < 200mg/kg if age < 6 years or < 150mg/kg if age > 6 years:
No intervention or drug level necessary.
Younger children appear to be less susceptible to hepatotoxicity.
Author:
Editor:
Dr Richard Aickin
Dr Richard Aickin
Paracetamol Poisoning
Service:
Date Issued
Children’s Emergency Dept
Reviewed April 2007
Page:
1 of 5
Starship Children’s Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.
PARACETAMOL POISONING
Maximum possible dose ≥200mg/kg if age < 6 years or > 150mg/kg if age > 6 years or when dose
is unknown / uncertain:
This includes most young people who present with ingestions as part of an episode of
intentional self harm, unless the presence of paracetamol can be clearly excluded on
history.
Ingestion of tablets / capsules: Serum paracetamol measurement at 4 hours post ingestion.
Ingestion of paracetamol elixir: Serum paracetamol measurement at 2 hours post ingestion.
(the 2 hour level should only relied upon in isolated paracetamol ingestions in well children).
• If the level is below the 4 hour treatment threshold (i.e. 1.0 mmol/L) at 2 hours then
it is safe to discharge the child with no treatment.
• If the level is above 1.0 mmol/L at 2 hours then a further level should be measured
at 4 hours (most of these children would not need treatment because the level will
be lower at 4 hours).
The following situations require consultation with senior staff:
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Chronic/repeated ingestions
Late presentation > 8 hours post ingestion
Unknown time of ingestion
Symptoms / signs of toxicity: Anorexia, nausea, vomiting, RUQ tenderness
If paracetamol level falls BETWEEN the upper and lower treatment lines – it may be
advisable to take a repeat level in 2 hours to establish a paracetamol half-life.
Further information is available via the Toxinz Website (www.toxinz.com)
Author:
Editor:
Dr Richard Aickin
Dr Richard Aickin
Paracetamol Poisoning
Service:
Date Issued
Children’s Emergency Dept
Reviewed April 2007
Page:
2 of 5
Starship Children’s Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.
PARACETAMOL POISONING
Nomogram
( Adapted from Smilkstein MJ et al. Ann Emerg Med 1991; 20: 1058-63)
CAUTION:
Ensure the correct units are used when applying plasma paracetamol results to the treatment
(Rumack-Mathew) nomogram. DO NOT confuse mmol/L with µmol/L, nor traditional units (mg/L)
with SI units (µmol/L).
The ADHB laboratory reports levels in µmol/L.
The left vertical scale on the nomogram is µmol/l (micromol/L).
Author:
Editor:
Dr Richard Aickin
Dr Richard Aickin
Paracetamol Poisoning
Service:
Date Issued
Children’s Emergency Dept
Reviewed April 2007
Page:
3 of 5
Starship Children’s Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.
PARACETAMOL POISONING
N-acetylcysteine (NAC)
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•
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•
Treatment with NAC is indicated for those children with levels above the threshold shown on
the nomogram.
At present there is no worldwide consensus on the safest paracetamol level at which to begin
treatment with NAC.
NAC is 100% effective at preventing hepatotoxicity if started within 8 hours of ingestion
Toxicity may still be reduced if it is started up to 24 hours after ingestion3
Delays in treatment with NAC can be associated with worse outcomes,1,2 . Therefore
treatment should be started immediately in children who present > 8 hours after a
significant ingestion or who are symptomatic of toxicity. Their further management
should then be discussed with a toxicologist / senior staff..
NAC dosing regime:
Standard therapy consists of a 20 hour course of IV N-acetylcysteine in 3 phases.
Phase 1: 150mg/kg over 15 minutes
Phase 2: 50mg/kg over 4 hours
Phase 3: 100mg/kg over 16 hours
In children N-acetylcysteine should be given intravenously as a 40 mg/mL solution in 5% dextrose
in water. This is to prevent possible hyponatremia.
Blood should be drawn for LFTS and PI/APPT at commencement of therapy.
Allergic reactions (flushing, urticaria, wheeze, angioedema, hypotension) / fever have been
commonly reported but are rarely severe5. They are dose dependant and usually occur during the
rapid administration of Phase 1.
Minor symptoms (flushing, urticaria) can be managed with hydrocortisone/ promethazine and
slowing (not stopping) the Phase 1 infusion such that it is completed over 1 hour.
More serious symptoms (angiooedema, wheeze, hypotension) require the infusion to be ceased
and symptoms managed appropriately (see Anaphylaxis guideline). 1 hour after symptoms have
abated the infusion can be restarted, with caution, at the slower rate (as above).
N-acetylcysteine therapy should not be stopped early even if a subsequent blood paracetamol level
shows a result now below the line predicting toxicity.
Risk Factors for Paracetamol Toxicity
•
Use of P450 2E1 inducing drugs e.g. phenobarbitone, carbamazepine
Induction of the P450 2E1 iso-enzyme leads to increased conversion of paracetamol to its
toxic metabolite NAPQI
•
Malnourishment, fasting, acute or chronic illness
Recent significant fasting or illness, such as eating disorders (e.g. anorexia nervosa), or
chronic illnesses such as HIV/AIDS may reduce intra-cellular glutathione levels increasing
toxicity of N-acetyl-p-benzoquinoneimine
•
Chronic alcoholism
Alcohol consumption at these levels may both induce iso-enzyme P450 2E1 and reduce
intra-cellular glutathione stores
Author:
Editor:
Dr Richard Aickin
Dr Richard Aickin
Paracetamol Poisoning
Service:
Date Issued
Children’s Emergency Dept
Reviewed April 2007
Page:
4 of 5
Starship Children’s Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.
PARACETAMOL POISONING
•
Gilbert’s syndrome, Crigler-Najjar syndrome
Individuals suffering these genetic defects may be at greater risk of paracetamol toxicity
References
1. Prescott LF, Illingworth RN, Critchley JA et al. Intravenous N-acetylcysteine: the treatment of
choice for paracetamol poisoning. Br Med J. 1979;2:1097-1100
2. Smilkstein MJ, Knapp GL, Kulig KW et al. Efficacy of oral N-acetylcysteine in the treatment of
acetaminophen overdose. Analysis of the national multicenter study (1976 to1985). N Engl J
Med. 1988;319:1557-1562
3. Keays R, Harrison PM, Wendon JA et al. IV N-acetylcysteine in paracetamol induced fulminant
hepatic failure: a prospective controlled trial. Br Med J. 1991;303:1026-1029
4. Reid D, Hazell W et al. Paracetamol poisoning: which nomogram should we use? Emerg Med.
2003; 15, 486-496
5. Bailey B, McGuigan M. Management of anaphylactoid reactions to intravenous Nacetylcysteine. Ann Emerg Med 1998; 31(6), 710-715
Author:
Editor:
Dr Richard Aickin
Dr Richard Aickin
Paracetamol Poisoning
Service:
Date Issued
Children’s Emergency Dept
Reviewed April 2007
Page:
5 of 5