These guidelines relate to adult patients only. For paediatric patients please use "Paracetamol XS Paediatrics" and discuss with your EM senior.
Background
- Hepatocellular necrosis is the major toxic effect
- Biochemical evidence of max. damage may not be until 72 - 96 hours post ingestion
- At risk dose is > 75mg paracetamol/kg body weight
- Severe liver damage = peak ALT > 1000 u/L
- Presentations > 12 hours post ingestion are more severely poisoned and at greater risk
- Acute renal tubular necrosis may also occur
- If there is doubt about the timing or the need for treatment - treat
- Methionine is ineffective in those given activated charcoal
- NAC is the treatment of choice>
High risk patients
- Regular alcohol ingestion
- Other enzyme (liver oxidase) inducers (e.g. carbamazepine, phenytoin, phenobarbitone, primidone and rifampicin)
- Glutathione depletion (e.g. malnutrition and HIV)
Do NOT take plasma levels within 4 hours of ingestion as they are unreliable.
- But patients may give inaccurate histories
- If in doubt, treat with NAC.
Staggered overdose (ingestion over >1hr)
- Toxicity may occur if >150 mg/kg ingested in any 24-hour period
- "Initial" Paracetamol levels are unhelpful so treat as OD
- Treat with NAC (as below) and admit to the CDU
Treatment nomogram
NAC Dosing per SNAP Protocol
Patients may give inaccurate histories. If in doubt, treat with NAC.
- Bag 1: 100 mg/Kg in 200 ml (NS or DW5) over 2 Hours
- Bag 2: 200 mg/Kg in 1000 ml (NS or DW5) over 10 Hours
- Check bloods (LFTs, INR, U&E, P&S, FBC) 2 hrs before bag 2 infusion due to end
Can discontinue after the 2nd bag if:
- INR ≤ 1.3 and
- ALT is normal and
- Paracetamol conc. < 10 mg/L and
- Patient has no symptoms suggesting liver damage
If all of these criteria are not met:
- Continue infusion with a 3rd bag of NAC at the same dose and rate as the 2nd. i.e. 200mg/kg over 10 hours
- Repeat bloods again after a further 10 hours of treatment
Stop treatment after 3rd bag (22 hours after commencing NAC) if:
- INR ≤ 1.3 and
- ALT < x2 upper limit of normal and
- ALT < x2 the admission measurement
If all of these criteria are not met:
- Continue infusion at same dose and rate
- Discuss with NPIS
- Discuss with Liver unit if not already involved
Specialist advice on those with liver disease.
Discuss (with liver unit) if any of below:
- ALT > 1000 u/L
- INR >3.0
- ↑ creatinine
- Acidosis or encephalopathy
- ↓BP (MAP < 60 mmHg)
- Pre-existing liver disease
Adverse reactions to NAC
- NAC adverse effects may be localised to infusion site or be more generalised
- Usually occur during the first 30 minutes of administration (large dose given rapidly)
- Include nausea, flushing, itching, erythematous rashes, urticaria, angioedema, bronchospasm and, rarely, ↑BP or ↓BP
- Infusion of NAC should be stopped and an antihistamine given
- Once adverse effects settled, resume infusion at the lowest infusion rate (200mg/kg over 10 hrs)
Links/References
- NHS Guidelines: https://nhslguidelines.scot.nhs.uk/media/1525/acetylcysteine-snap-protocol-for-treatment-of-paracetamol-overdose.pdf
- Supporting: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30066-5/fulltext
- TOXBASE (Check resusc. room PC for login details) (Toxbase email)
- Phone at The National Poisons Information Service (01 8092566) Fax: 01 8368476
- Members of the public 01 8092166 or https://poisons.ie
- The BNF is also available on line