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Title: Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen.
Austin Authors: Wong, Anselm ;Sivilotti, Marco L A;Gunja, Naren;McNulty, Richard;Graudins, Andis 
Affiliation: Department of Medicine, School of Clinical Sciences, Monash University, Victoria, Australia
Departments of Emergency Medicine and Biomedical & Molecular Sciences, Queen's University, Kingston, Canada
Westmead and Blacktown Hospitals, Western Sydney Toxicology Service, Sydney, Australia
Monash Toxicology Service, Monash Health, Dandenong, Australia
Austin Toxicology Service, Austin Health, Heidelberg, Victoria, Australia
Victorian Poisons Information Centre, Austin Health, Heidelberg, Victoria, Australia
Issue Date: Mar-2018 2017-07-31
Publication information: Clinical Toxicology 2018; 56(3): 182-188
Abstract: Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol-aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen. We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L). Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase. The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens.
DOI: 10.1080/15563650.2017.1355058
ORCID: 0000-0002-6817-7289
PubMed URL: 28756679
Type: Journal Article
Subjects: Acetaminophen
liver injury
risk prediction
Appears in Collections:Journal articles

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