Paracetamol overdose is a common presentation in A&E and so you may often find yourself looking after them. The information below is to help give you an overview.
- Excellent analgesia and antipyretic.
- Recommended paracetamol dose in adults = 4g or 75mg/kg in 24h.
- Overdose = ingestion >75mg/kg.
- >150mg/kg = Lethal.
- Special circumstances:
- Pregnancy – Toxic dose calculated using the patient’s pre-pregnancy weight.
- Weight >110kg – Toxic dose calculated with a max weight of 110kg.
- Signs and symptoms of overdose:
- Paracetamol metabolism: 20% in the small intestines, 80% by the liver.
- The toxic metabolite, NAPQI is formed in paracetamol overdose.
- NAPQI is inactivated by glutathione.
- ↓ glutathione storage with ↑ NAPQI during paracetamol overdose.
- Build-up of NAPQI causes toxicity in centrilobular hepatocytes.
Important questions to ask
- Time since overdose
- Amount ingested
- Single-dose or staggered?
- Intentional or accidentally?
- Any other medications/substance taken?
- Any alcohol ingestion?
- Assess suicidal risk. Involve the mental health team.
- NAC is a precursor for glutathione.
- Protects against paracetamol-induced hepatoxicity by restoring glutathione levels.
- Treatment must be started within 8h of ingestion to achieve maximum protection.
- If the patient has a reaction, discuss with seniors. Usually only stopped in anaphylaxis. Otherwise, symptomatic management of rash with anti-histamines and monitor
- Full treatment course varies by hospital. Typically, 3 consecutive IV infusions (or more if liver derangement) lasting around 20 hours
- NAC causes a drop in vitamin K dependent factors, effects last throughout the infusion. Therefore, INR of 1.2-1.3 is common after treatment.
Management: (Treatment goal is to prevent/minimise liver injury)
Single-dose or ingestion <1 h.
Management is guided by plasma paracetamol concentration at ideally 4 hours
- Consider activated charcoal (usually 50g orally or 1g/kg for children) in patients with significant overdose. The cut off depends on local guidelines
- At 4 hours, take bloods including paracetamol level, UEs, creatinine, bicarbonate, LFTs, INR, FBC. Assess the risk of liver damage from plasma paracetamol concentration/time on the nomogram. If it is above or on the nomogram it is treated with NAC.
- Bloods as above, but if levels are not back within 8h since overdose, start NAC
- Bloods as above. NAC is started if evidence of toxic dose within 24 hours. If >24h then depending on the presence of liver derangement (jaundice, RUQ tenderness, deranged INR/LFTs) or if detectable paracetamol level
Staggered overdose (ingestion over >1h).
- Usually, NAC is started immediately if >75mg/kg ingested
- Bloods: paracetamol level, UEs, creatinine, bicarbonate, LFTs, INR, FBC on arrival.
- It might be stopped if the bloods are unremarkable.
- All patients should be reviewed by the psychiatry team prior to discharge
- Inform seniors if
- there is a risk of self-discharge
- the patient is symptomatic (although obvious, avoid giving paracetamol for pain!)
- derangement of bloods
Criteria for referral to a specialist unit
- Encephalopathy/Raised ICP.
- INR >2.0 at or before 48 hours or >3.5 at or before 72 hours.
- Renal impairment (Creatinine >200 μmol/L).
- Blood pH <7.3 or bicarbonate <18 mmol/L.
- Systolic BP <80 mmHg despite adequate fluid resuscitation.
- Further reading:- King’s College Hospital criteria for liver transplantation in paracetamol-induced acute liver failure.
Written by Dr Amelia Lim (FY2)
With thanks to Dr Zi Yi Tew (CT1)
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