Paracetamol is widely available without prescription
As a result is one of the more common overdoses seen in hospital
It is also one of the most common causes of death associated with overdose
Pathophysiology
Paracetamol is normally converted to non-toxic metabolites, with only 5% converted into a toxic NAPQI
In overdose, the normal pathways become overwhelmed and more toxic NAPQI is created with insufficient amounts of glutathione to bind it and make it non-toxic
High levels of NAPQI cause liver cell damage and necrosis
Acetylcysteine reduces paracetamol toxicity by increasing availability of glutathione
Initial Assessment
Non-staggered ingestion
If all of the paracetamol was taken within an hour this is considered a non-staggered overdose and a paracetamol level after 4 hours can help guide the need for treatment, using the nomogram
If there are adverse features like deranged LFTs or renal impairment at presentation consider treatment despite levels
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| Original source: bnf.nice.org.uk |
Staggered ingestion
Consider treatment irrespective of blood test results
Toxicity is less concerning if total dose less than 150mg/kg but may still require treatment depending
on presentation and other results
Baseline Investigations
Paracetamol level, renal profile, LFTs, INR, FBC
Consider ECGs and other investigations in cases of mixed overdose
Treatment
Although there are oral options for treatment, in hospital management of paracetamol overdose is almost exclusively with N-acetylcysteine (NAC)
10-20% of patients develop hypersensitivity reactions which can mimic anaphylaxis (itching, rash, swelling, respiratory distress, low blood pressure). These patients should be urgently assessed
Nausea and vomiting are common and can usually be managed symptomatically
Consider steroids and antihistamines who have previously had reactions
Treatment is most commonly administered as per the guidance from the BNF, using 1h, 4h and 16h infusions with N-acetylcysteine dosing based upon patient weight
There is increasing literature to suggest that accelerated administration may be possible without increased risk to patients, for example the SNAP 12h Acetylcysteine Regimen
Assessing response to treatment
Blood tests (LFTs, INR, renal profile) should be repeated before completion of 3rd bag, and prior to completion of subsequent bags if needed
Worrying features include rising ALT and/or INR and this may require further treatment with NAC
Rising lactate, deranged renal function and hypoglycaemia are all associated with adverse outcomes
Note: some analysers significantly underestimate paracetamol levels when taken during NAC infusion and this may therefore not be helpful
Where LFTs and clotting continue to deteriorate despite treatment, NAC should be continued and discussions may need to be had with a specialist liver unit, such as Kings College, London
Acute mental health crises
Although paracetamol overdoses can occur due to excessive therapeutic use or other error, healthcare professionals will most commonly encountner paracetamol toxicity in the context of intentional overdose with intent to self harm or end one's life
It is important to give consideration at to the ongoing risk felt to be associated with this act or other behaviours exhibited during the course of clinical assessment i.e. ongoing suicidal ideations
Ensure that local processes are observed to ensure that an adequate mental health assessment is made
Within the UK, many hospitals with have a psychiatric liaison service
When a patient attempts to leave prior to such an assessment, risk and capacity should be assessed and it may be felt necessary to put a legal framework in place to detain the individual. In the UK, this would be under the Mental Health Act (often a Section 5(2) when the patient is under the care of a medical team, rather than psychiatric service)
Note that Section 5(2) of the Mental Heath Act does not allow a team to treat a person for their overdose and a concurrent assessment of their capacity should occur to determine whether the patient should be treated under the Mental Capacity Act, and in their best interests
These can be very difficult decisions to make and, as such, seek support from colleagues including the mental health team is encouraged to ensure the right decision is made for any given patient
Learning Points
- Assess need for treatment through history and baseline bloods (paracetamol level, INR, LFTs, renal profile, FBC)
- Ensure treatment is prescribed appropriately based upon weight
- Repeat blood tests should be undertaken before completion of 16h bag
- Treatment should continue until we are satisfied that blood tests are improving
- When LFTs, INR and other measures deteriorate despite treatment, advice should be sought from a specialist liver unit
Additional Resources
British National Formulary bnf.nice.org.uk
Toxbase toxbase.org
The Mental Heath Act 1983 www.mind.org.uk/information-support/legal-rights/mental-health-act-1983
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