Retrospective evaluation of repeated supratherapeutic ingestion (RSTI) of paracetamol

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

Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand

“…Patients who meet the criteria for supratherapeutic ingestion (Box 1) should have the paracetamol concentration and ALT measured. There is evidence that the combination of a low paracetamol concentration and normal ALT at any time indicates there is minimal risk of subsequent hepatotoxicity . If the paracetamol concentration is greater than 20 mg/L (132 μmol/L) or ALT is greater than 50 U/L, then acetylcysteine is commenced, and pathology repeated 8 hours after the initial sampling.…”

“…Acetylcysteine can be ceased at this stage if the paracetamol concentration is less than 10 mg/L and ALT is less than 50 U/L or static. Patients with significant acute liver injury secondary to paracetamol will have a very high and/or rapidly rising ALT . Small fluctuations in ALT (eg, ± 20 U/L or ± 10%) are common and do not on their own indicate the need for ongoing acetylcysteine.…”

Using a decision tree algorithm to distinguish between repeated supra-therapeutic and acute acetaminophen exposures

“…Our study found that most RSTI exposures tend to produce aminotransferase concentrations between 100 and 1,000 IU/L or greater than 1,000 IU/L. Prior studies have found that all cases with RSTI who developed hepatotoxicity were found to have abnormal ALT (more than 50 IU/L) [ 8 ] and more likely to have encephalopathy requiring renal replacement therapy, mechanical ventilation, or death [ 21 ]. The risk of liver failure has also been seen in patients with RSTI compared to acute overdose cases [ 22 ].…”

“…There are few studies and guidelines vary in what constitutes RSTI and when to start N-acetylcysteine. Typically, N-acetylcysteine is recommended in patients with alanine aminotransferase (ALT) greater than 50 IU/L or serum acetaminophen concentration greater than 20 mg/L (132 µmol /L) [ 8 , 9 ]. Daly et al studied 249 RSTI of acetaminophen and found that patients with AST < 50 U/L and acetaminophen concentrations less than 10 mg/L had a lower risk of hepatotoxicity [ 10 , 11 ].…”

The changing face of paracetamol toxicity and new regimens for an old antidote acetylcysteine

“…10 Another important scenario is repeated supratherapeutic therapeutic ingestions of paracetamol 11,12 and daily use, 13 arising in numerous situations in which paracetamol is being used as an analgesic. This can cause both short-term toxicity requiring modified regimens of acetylcysteine 14 but also may cause cardiovascular adverse effects and increased risk of gastrointestinal bleeding with daily use for long periods of time. 13 Prescribers need to be aware that such chronic paracetamol use is not benign, and with good evidence for side-effects, alternative analgesics may be more appropriate.…”