Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen

INTRODUCTION: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:56

Enthalten in:

Clinical toxicology (Philadelphia, Pa.) - 56(2018), 3 vom: 22. März, Seite 182-188

Sprache:

Englisch

Beteiligte Personen:

Wong, Anselm [VerfasserIn]
Sivilotti, Marco L A [VerfasserIn]
Gunja, Naren [VerfasserIn]
McNulty, Richard [VerfasserIn]
Graudins, Andis [VerfasserIn]

Links:

Volltext

Themen:

362O9ITL9D
Acetaminophen
Acetylcysteine
Analgesics, Non-Narcotic
Antidotes
Journal Article
Liver injury
Risk prediction
WYQ7N0BPYC

Anmerkungen:

Date Completed 06.05.2019

Date Revised 09.04.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/15563650.2017.1355058

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM274310333