Recent management and improved outcomes for modified release paracetamol overdose

Abstract

Background: Modified-release paracetamol overdose often requires prolonged treatment, with some developing liver injury despite early acetylcysteine. ATOM-3, a study of 116 modified-release paracetamol overdoses, reported hepatotoxicity in 21 (18%), including six treated within 8 h. Following this study, Australian guidelines recommended a 20 h course of acetylcysteine for all toxic modified-releaseingestions, with increased dosing for doses >30 g or high initial paracetamol concentration, some adopted these changes earlier. The objective was to assess the rate of hepatotoxicity (alanine aminotransferase >1,000 U/L) in modified-release paracetamol overdoses following practice change.Methods: This retrospective series included patients from two Poisons Information Centres and three toxicology units (July 2017-December 2023) following an acute toxic ingestion of modified-release paracetamol. Data collection included demographics, treatment, and hepatotoxicity rates.Results: In total, 243 patients were identified (175 [72%] female, median age 26 years [IQR: 17-51]). The median ingested dose was 23.9 g (IQR: 16.0-38.6), and median time to presentation of 4.6 h (IQR: 1.8-12.3 h) post-ingestion. Activated charcoal was administered in 74 (67%) patients at a median time of 3.8 h post-ingestion (IQR: 2.0-7.3 h), with 10 having more than one dose. Acetylcysteine was administered to 238 (98%) patients at a median time of 6.8 h (IQR: 4.1-13.6 h) post-ingestion. Increased dose acetylcysteine was administered in 100, and 80 received extended acetylcysteine beyond 20 h. Criteria for increased acetylcysteine was met in 122 (50%) patients, with either/both an ingested dose >30 g (n = 89) or an initial paracetamol concentration > double the 150 mg/L at 4 h nomogram line (n = 71). Of these, 85 (70%) received an increased dose of acetylcysteine. Thirty (12%) developed hepatotoxicity, including four with alanine aminotransferase >1,000 U/L at presentation. No patients treated with acetylcysteine within 8 h developed hepatotoxicity. Two late presenters (>48 h post-ingestion) died.Conclusions: This study found less hepatotoxicity in early presenters compared to the ATOM-3 study. These findings suggest that changes to the guideline may have reduced hepatotoxicity risk in modified-release paracetamol overdose.