Retrospective evaluation of repeated supratherapeutic ingestion (RSTI) of paracetamol

• Published in: Clinical toxicology (Philadelphia, Pa.) Vol. 57; no. 8; pp. 703 - 711
• Main Authors: Egan, Harry, Isbister, Geoffrey K., Robinson, Jennifer, Downes, Michael, Chan, Betty S., Vecellio, Elia, Chiew, Angela L.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.08.2019
• Subjects: Acetaminophen - administration & dosage; Acetaminophen - blood; Acetaminophen - therapeutic use; acetylcysteine; Acetylcysteine - administration & dosage; Acetylcysteine - therapeutic use; Adult; Alanine Transaminase - blood; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - blood; Analgesics, Non-Narcotic - therapeutic use; Chemical and Drug Induced Liver Injury - blood; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - epidemiology; Drug Overdose - blood; Drug Overdose - drug therapy; Drug Overdose - epidemiology; Female; hepatotoxicity; Humans; Male; Middle Aged; Paracetamol; Retrospective Studies; acetylcysteine; Paracetamol; hepatotoxicity
• ISSN: 1556-3650; 1556-9519
• DOI: 10.1080/15563650.2018.1547829

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.