Division of Clinical Pharmacology

This information summary is based on the Consensus Statement published in the Medical Journal of Australia (Daly FFS et al, MJA 2008;188(5):296-301, www.mja.com). For full information please refer to this publication.

Note About Units: Serum paracetamol is measured at some laboratories, including SydPath, in mg/L. Some laboratories report in umol/L. Ensure that the correct scale on the nomogram is used to interpret results. To convert results in umol/L to mg/L multiply result by 0.15.

Initial considerations

Any patient with paracetamol ingestion above those amounts indicated in Table 1 should be considered at risk of severe liver injury. Patients below these thresholds without deliberate self-poisoning are at low risk and do not require paracetamol levels, LFT or follow-up.

Regardless of paracetamol dose, all patients with paracetamol deliberate self-poisoning should have serum paracetamol level measured.

Additional Information

Signs consistent with paracetamol poisoning include: nausea, vomiting, abdominal tenderness in the right upper quadrant or mental status changes.

Predisposing risk factors which might increase the risk of liver injury include:

• Chronic alcohol abuse
• Taking microsomal inducing drugs such as barbiturates, carbamazepine, rifampicin and isoniazid (not phenytoin)
• Likely glutathione depletion (prolonged fasting or vomiting, dehydration, anorexia nervosa, bulimia, malnutrition caused by other factors such as HIV or malignancy)
• Other causes of liver injury (eg viral or alcoholic hepatitis)

Recommended management of Acute Overdose
See below for other settings: unknown time of ingestion; staggered overdose; sustained release preprations; repeated supratherapeutic ingestions.

Presentation within 1 hour of overdose with ingestion of high risk levels:

Use activated charcoal if patient is adult, co-operative and has history of ingestion greater than 10g or 200 mg/kg (whichever is less). Measure paracetamol at 4 hours and manage based on results as indicated below.

Presentation between 1 and 8 hours of overdose with ingestion of high risk levels:

Measure plasma paracetamol between 4 and 8 hours of ingestion. Plot paracetamol on teatment nomogram. If BELOW treatment line - medical treatment not required. If ABOVE treatment line commence NAC infusion

Presentation more than 8 hours after ingestion with ingestion of high risk levels:

Treat with NAC if history indicates high risk levels or patient shows signs suggestive of toxicity (delay in NAC treatment beyond 8 hours is the most important prognostic factor after acute overdose). Measure plasma paracetamol, ALT, INR and FBC. If paracetamol ABOVE treatment line on nomogram or ALT elevated - continue NAC infusion and follow up with repeat ALT at end of infusion. If Paracetamol is BELOW treatment line and ALT is normal or falling, cease NAC.

Paracetamol Treatment Nomogram

Conditions where the nomogram does not apply

Unknown Time of paracetamol ingestion

If there is a detectable paracetamol with an unknown time of ingestion, commence NAC and treat the patient as a patient with acute ingestion presenting after more than 8 hours.

Multiple or "staggered" Overdose

If there were several ingestions over a period of less than 24 hours, interpret nomogram as though all paracetamol was taken at the time of the earliest dose. If it is over 8 hours since the first dose treat patient according to >8 hours scenario above.

Sustained release Paracetamol preparations.

Treat patient with NAC if dose is either >10 g or >200 mg/kg. Measure paracetamol at 4 hours after ingestion and again 4 hours later if first result is below treatment line on nomogram. If both results are below treatment line NAC may be discontinued.

Repeated supratherapeutic ingestions.

If above high risk dose levels as per table 1 measure plasma paracetamol and ALT. If ALT is normal and serum paracetamol is less than 20 mg/L (120 umol/L), no further action is required. If either ALT is elevated or paracetamol is higher than 20 mg/L (120 umol/L) commence NAC infusion. Repeat ALT and paracetamol after 8 hours infusion - if ALT stable or falling, cease NAC infusion.

Protocol for Treatment with N-acetyl cysteine (NAC) (Parvolex)

Initial Dose:      150 mg/kg IV in 200 ml 5% dextrose over 15 - 60 minutes
Second Dose:    Follow initial infusion with 50 mg/kg IV in 500 mL 5% dextrose over 4 hours
Third dose:        Follow 2nd infusion with 100 mg/kg IV in 1000 mL 5% dextrose over 16 hours

Contraindications to NAC: Hypersensitivity or previous anaphylactic reaction to acetylcysteine. Parvolex is not compatible with rubber and metals.
Adverse Effects:  Rash, bronchospasm and anaphylaxis which may be severe. 
NOTE: anaphylactoid reactions manifested by rash, wheeze or mild hypotension occur in 10% - 50% of patients and may be treated with antihistamines and temporarily halting or slowing the rate of infusion.