Treatment regimen for initial acetylcysteine therapy

For advice on when to start acetylcysteine therapy and the appropriate dosage regimen after an acute ingestion of modified-release paracetamol, see Indications for acetylcysteine therapy following acute ingestion of modified-release paracetamol. The initial regimen for acetylcysteine therapy is a two-bag infusion over 20 hours. The first bag is infused over 4 hours and the second over 16 hours1. The dose of the second infusion depends on the serum paracetamol concentration.

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 hours2 modified-release paracetamol poisoning - standard-dose regimen

FOLLOWED BY

acetylcysteine 100 mg/kg (up to 11 g) in crystalloid solution 1000 mL intravenously, over 16 hours2.

For children, use:

acetylcysteine 200 mg/kg in crystalloid solution 7 mL/kg (up to 500 mL) intravenously, over 4 hours2

FOLLOWED BY

acetylcysteine 100 mg/kg in crystalloid solution 14 mL/kg (up to 1000 mL) intravenously, over 16 hours2.

Two hours before completing the second infusion, repeat the serum ALT and paracetamol concentrations to check if an extended acetylcysteine regimen is required.

High-dose acetylcysteine regimen

If high-dose acetylcysteine therapy is indicated, for adults, use:

acetylcysteine 200 mg/kg (up to 22 g) in crystalloid solution 500 mL intravenously, over 4 hours3 modified-release paracetamol poisoning - high-dose regimen

FOLLOWED BY

acetylcysteine 200 mg/kg (up to 22 g) in crystalloid solution 1000 mL intravenously, over 16 hours3.

For children, use:

acetylcysteine 200 mg/kg in crystalloid solution 7 mL/kg (up to 500 mL) intravenously, over 4 hours3

FOLLOWED BY

acetylcysteine 200 mg/kg in crystalloid solution 14 mL/kg (up to 1000 mL) intravenously, over 16 hours3.

Two hours before completing the second infusion, repeat the serum ALT and paracetamol concentrations to check if extended acetylcysteine therapy is required.

Extended acetylcysteine regimen

Note: If the patient has evidence of acute liver injury or hepatotoxicity following ingestion of modified-release paracetamol, seek advice from a clinical toxicologist or liver transplant unit.

Some patients with modified-release 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 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)4
  • serum paracetamol concentration 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 an extended acetylcysteine regimen, for adults use:

acetylcysteine 100 mg/kg (up to 11 g) in crystalloid solution 1000 mL intravenously, over 16 hours5. modified-release paracetamol poisoning - extended regimen

For children, use:

acetylcysteine 100 mg/kg in crystalloid solution 14 mL/kg (up to 1000 mL) intravenously, over 16 hours5.

If the patient has evidence of acute liver injury or hepatotoxicity after modified-release 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 is lower than 10 mg/L (66 micromol/L)
  • the patient is clinically well.
1 Compared with the three-bag infusion regimen that was used previously, the two-bag infusion regimen reduces the risk of dosing errors and is associated with fewer immediate immune-mediated (non-IgE) hypersensitivity reactions.Return
2 Acetylcysteine is compatible with the following crystalloid solutions: sodium chloride 0.9% and glucose 5%.Return
3 Acetylcysteine is compatible with the following crystalloid solutions: sodium chloride 0.9% and glucose 5%.Return
4 Patients with significant acute liver injury have a high or rapidly rising serum ALT concentration. Small fluctuations in ALT (eg 20 U/L or 10%) are common and do not on their own indicate the need for ongoing acetylcysteine therapy.Return
5 Acetylcysteine is compatible with the following crystalloid solutions: sodium chloride 0.9% and glucose 5%.Return