Guidelines for the management of paracetamol poisoning in Australia and New Zealand — explanation and elaboration

Abstract

Paracetamol is involved in a large proportion of accidental paediatric exposures and deliberate self‐poisoning cases, although subsequent hepatic failure and death are both uncommon outcomes. The optimal management of most patients with paracetamol overdose is usually straightforward. However, several differing nomograms and varying recommendations regarding potential risk factors for hepatic injury introduce complexity. In order to reconcile management advice with current Australasian clinical toxicology practice, revised guidelines have been developed by a panel of clinical toxicologists consulting to the poisons information centres in Australia and New Zealand using a workshop and consultative process. This article summarises the rationale for the recommendations made in these new guidelines.

Paracetamol-associated acute liver failure in Australian and New Zealand children: high rate of medication errors

“…Pharmacokinetic properties are altered in staggered overdoses, which can be further compounded by the coadministration of over-the-counter preparations containing paracetamol or drugs capable of inducing hepatic microsomal enzymes 1. In addition to the uncertainty of drug dosages and timing provided by historians, the kinetics of tablet, capsule and liquid preparations also adds to this complexity, with peak concentrations within 1–2 h for standard tablets or capsule formulations and within 30 min for liquid preparations 1 11. Another consideration and limitation of this study was the possibility of having attributed events to adverse drug reactions when they are in fact a consequence of substandard preparations 14 15.…”

“…Acute liver failure was attributed to paracetamol overdose in instances where there was a documented history of paracetamol ingestion that fulfilled either of the following criteria: cumulative dose greater than 150 mg/kg ingested within 8 h1 ≥2 doses ingested over a period greater than 8 h resulting in a toxic cumulative dose with no other cause identified 1 …”

Theme: Paracetamol (acetaminophen) poisoning

“…Administration of NAC within 8 h of an acute ingestion guarantees survival 2. Although activated charcoal, if administered early, has been shown to reduce serum levels and the number of patients requiring NAC, it does nothing to improve survival if NAC is administered within 8 h 3.…”

“…This widely accepted threshold for possible hepatotoxicity in acute ingestions of standard preparations is a reasonable, conservative treatment threshold for sustained release preparations. Although the standard nomograms do not strictly apply to sustained release ingestions, it has been recommended that if both 4 and 8 h levels are below treatment threshold then treatment may be stopped 2. An alternative approach is discussed in Goldfrank's 4…”

N‐Acetyl cysteine does not prevent liver toxicity from chronic low‐dose plus subacute high‐dose paracetamol exposure in young or old mice

“…NAC guidelines are designed for protection from a single high dose of paracetamol and there is little evidence to guide risk assessment and optimal treatment for staggered over-exposures, chronic exposure or repeated supra-therapeutic exposures (18). One animal study found that several weeks of NAC pre-treatment protected against toxicity induced by twice-weekly paracetamol dosing (19).…”