Retrospective evaluation of repeated supratherapeutic ingestion (RSTI) of paracetamol^†

† Meetings: This work has been presented at the following conferences and early results published in abstract form for these conferences:

Abstract

Background: Repeated supratherapeutic ingestion (RSTI) of paracetamol can result in acute liver injury. Management guidelines vary worldwide and in Australia, acetylcysteine treatment is recommended in patients with a paracetamol concentration ≥20 mg/L and/or alanine transaminase (ALT) ≥50 U/L.

Objectives: To investigate patients with RSTI of paracetamol and determine whether admission ALT <50 U/L rules out those who develop hepatotoxicity (ALT >1000 U/L).

Method: Retrospective review of paracetamol RSTI presentations to two toxicology services over a four-year period. Patients were included if they ingested >4 g per 24 h of paracetamol for a period >8 h, regardless of intent. Data collected included demographics, ingestion history, pathology results, treatments and outcomes.

Results: 266 patients were identified with median ingested dose of 9 g per 24 h (IQR: 6–12 g) over a median of 2 days (IQR: 1–5 days). On presentation, paracetamol was detected in 192 (72%), with median concentration of 14 mg/L (IQR: 7–27 mg/L). Median ALT on admission in those developing hepatotoxicity was significantly higher, 1182 U/L (IQR: 598–4251 U/L), compared to 30 U/L (IQR: 18–59 U/L; p < .0001) in those who did not. All 17 who developed hepatotoxicity had an ALT ≥50 U/L on presentation. Five patients presenting with an ALT <50 U/L developed a peak ALT between 50 and 1000 U/L, of which three had a paracetamol concentration <20 mg/L. 139 (52%) received acetylcysteine, of which 64 received an abbreviated course (<20 h), with a median length of infusion of 11 h (IQR: 7–14 h). 127 (48%) patients were not treated with acetylcysteine, none of these patients returned to hospital.

Conclusions: Our results confirm that those developing hepatotoxicity from RSTI of paracetamol have an elevated ALT on presentation. Presenting ALT <50 U/L appears to be a safe threshold not to administer acetylcysteine, provided the paracetamol concentration is low.

Keywords:

• Paracetamol
• hepatotoxicity
• acetylcysteine

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Geoffrey Isbister is funded by an National Health and Medical Research Council (NHMRC) Senior Research Fellowship ID1061041.