Antidote: acetylcysteine
Indications for acetylcysteine therapy
In cases of unintentional paracetamol poisoning (also referred to as repeated supratherapeutic ingestion [RSTI]), a standard-dose acetylcysteine regimen is indicated if the:
- initial serum paracetamol concentration is 20 mg/L (132 micromol/L) or higher
- initial serum ALT concentration is 50 U/L or higher
- patient is symptomatic and investigation results will be delayed by more than 2 hours after presentation.
The standard-dose acetylcysteine regimen is a two-bag infusion given over 20 hours1. The first bag is infused over 4 hours and the second over 16 hours.
If the initial serum ALT concentration is 1000 U/L or higher (ie evidence of hepatotoxicity), complete the full 20-hour standard-dose acetylcysteine regimen irrespective of the dose ingested or subsequent investigations.
If the initial serum ALT concentration is below 1000 U/L, measure the serum ALT and paracetamol concentrations at least 8 hours after the initial measurement. The acetylcysteine infusion can be stopped early if both of the following criteria are met:
- serum paracetamol concentration is lower than 10 mg/L (66 micromol/L)
- serum ALT concentration is lower than 50 U/L or not rising.
Some patients require an extended acetylcysteine regimen beyond the 20-hour regimen because they are at greater risk of developing acute liver injury. To determine the need for an extended acetylcysteine regimen, measure the serum ALT and paracetamol concentrations 2 hours before completion of the 20-hour acetylcysteine regimen in all patients.
An extended acetylcysteine regimen is warranted if the:
- serum ALT concentration is higher than 50 U/L or serum ALT concentration has increased in patients who had a baseline serum ALT concentration of 50 U/L or higher (eg in patients with pre-existing liver biochemistry abnormalities)2
- serum paracetamol concentration is higher than 10 mg/L (66 micromol/L)3.
If the serum ALT concentration is high despite treatment, but is not rapidly rising, investigate for other causes of hepatotoxicity.
Standard-dose acetylcysteine regimen
If standard-dose acetylcysteine therapy is indicated, for adults, use:
acetylcysteine 200 mg/kg (up to 22 g) in crystalloid solution 500 mL intravenously, over 4 hours4 unintentional paracetamol poisoning - standard-dose regimen
FOLLOWED BY
acetylcysteine 100 mg/kg (up to 11 g) in crystalloid solution 1000 mL intravenously, over 16 hours4.
For children, use:
acetylcysteine 200 mg/kg in crystalloid solution 7 mL/kg (up to 500 mL) intravenously, over 4 hours4
FOLLOWED BY
acetylcysteine 100 mg/kg in crystalloid solution 14 mL/kg (up to 1000 mL) intravenously, over 16 hours4.
Two hours before completing the second infusion, repeat the serum ALT and paracetamol concentrations to check if an extended acetylcysteine regimen is required.
Extended acetylcysteine regimen
Some patients with unintentional paracetamol poisoning require an extended acetylcysteine regimen beyond the 20-hour regimen because they are at higher risk of developing acute liver injury. To determine the need for an extended acetylcysteine regimen, measure the serum ALT and paracetamol concentrations 2 hours before completion of the 20-hour acetylcysteine regimen in all patients. An extended acetylcysteine regimen is warranted in patients in whom:
- serum ALT concentration is higher than 50 U/L or increased serum ALT concentration in patients who had a baseline serum ALT concentration of 50 U/L or higher (eg in patients with pre-existing liver biochemistry abnormalities)5
- serum paracetamol concentration is higher than 10 mg/L (66 micromol/L)—consult a clinical toxicologist if the repeat serum paracetamol concentration is higher than 100 mg/L (660 micromol/L); an extended regimen with a higher dose of acetylcysteine may be required.
If the patient meets the criteria for extended acetylcysteine therapy, for adults, use:
acetylcysteine 100 mg/kg (up to 11 g) in crystalloid solution 1000 mL intravenously, over 16 hours6. unintentional paracetamol poisoning - extended regimen
For children, use:
acetylcysteine 100 mg/kg in crystalloid solution 14 mL/kg (up to 1000 mL) intravenously, over 16 hours6.
If the patient has evidence of acute liver injury or hepatotoxicity after unintentional paracetamol poisoning, seek advice from a clinical toxicologist or liver transplant unit. Patients on an extended acetylcysteine regimen need regular clinical review and blood tests every 12 hours (or more often if their condition deteriorates). If the patient has abnormal liver biochemistry, perform prognostic blood tests (eg concentrations of electrolytes, urea, creatinine, glucose, lactate and phosphate; liver biochemistry; INR; blood gas analysis). See advice on liver failure below.
Continue acetylcysteine therapy until the following four conditions are met:
- serum ALT concentration is decreasing
- INR is lower than 2.0
- serum paracetamol concentration lower is than 10 mg/L (66 micromol/L)
- the patient is clinically well.
Immediate immune-mediated (non-IgE) hypersensitivity reactions to acetylcysteine
Acetylcysteine is generally well tolerated, but occasionally immediate immune-mediated (non-IgE) hypersensitivity reactions can occur—reactions include rash, urticaria, flushing, and (rarely) bronchospasm and hypotension. If symptoms occur, stop the infusion, treat the reaction as required with antihistamines and bronchodilators, and restart the infusion when the reaction subsides. This reaction does not indicate an allergy or contraindicate further treatment with acetylcysteine.
See also Anaphylaxis for management of immediate immune-mediated (non-IgE) hypersensitivity reactions.