Received 28 January 2026, accepted 28 January 2026
- Anselm Wong, Richard McNulty, Sarah E. Hodgson, Naren Gunja, Andis Graudins
Correspondence: anselm.wong@austin.org.au
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Abstract
Objectives
To determine whether ceasing acetylcysteine treatment for adults with acute paracetamol overdose after at least 12 h of the two-bag acetylcysteine regimen is non-inferior to providing the full 20-h two-bag regimen.
Study Design
Open label, non-inferiority randomised controlled trial.
Setting
Emergency departments of six Australian metropolitan hospitals (four in Melbourne, two in Sydney), 1 December 2019–31 July 2024.
Participants
Adults who required acetylcysteine treatment following single or staggered paracetamol ingestions whose serum alanine transaminase (ALT) level was below 40 IU/L on presentation, and whose ALT levels were below 40 IU/L and serum paracetamol concentrations below 20 mg/L after 12 h of acetylcysteine treatment.
Intervention
Control group (standard care): two-bag intravenous acetylcysteine regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h). Intervention group: Acetylcysteine stopped at least 12 h after treatment initiation and the 20-h infusion period completed with intravenous compound sodium lactate.
Main Outcome Measures
Difference in ALT level between presentation and 20 h after acetylcysteine treatment initiation; non-inferiority was defined as the upper limit of the 95% confidence interval (CI) of the difference between median changes in ALT level for the intervention and control groups being less than 3 IU/L.
Results
Of 2830 people who presented with paracetamol overdose, 860 received acetylcysteine treatment; 186 people who met both the presentation and 12-h acetylcysteine treatment blood test inclusion criteria (median age, 17 years; interquartile range [IQR], 16–23 years; 162 women [87%]) were randomly assigned to the intervention (93 participants) and control groups (93 participants). Median acetylcysteine infusion time in the intervention group was 13 h (IQR, 13–13 h). The median change in ALT level between arrival and 20 h after starting intravenous acetylcysteine treatment was similar for the intervention (−1 IU/L; IQR, −4 to 1 IU/L) and control groups (0 IU/L; IQR, −2 to 2 IU/L); the difference in median change (−1 IU/L; 95% CI, −2 to 1 IU/L) was consistent with the non-inferiority criterion. No patients developed hepatic injury or hepatotoxicity.
Conclusion
An abbreviated acetylcysteine treatment regimen was non-inferior to the standard 20-h two-bag regimen for people with paracetamol overdose who were at low risk of hepatic failure.
Trial Registration
ACTRN12619001549112 (prospective)