Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose

Abstract

Context There is contention over whether reported dose correlates with toxicity in paracetamol poisoning and risk assessment is currently based on serum paracetamol concentration compared to a nomogram, irrespective of reported dose.ObjectiveTo determine if reported dose predicts the need for N-acetylcysteine (NAC).MethodsData were taken from paracetamol overdoses presenting to a tertiary toxicology service. Age, sex, reported dose, ingestion time, timed paracetamol concentrations between 4 and 16 h, hepatotoxicity (peak alanine transaminase > 1000 U/L) and treatment (single dose-activated charcoal [SDAC] and NAC) were analysed. Data were analysed within a repeated measures logistic regression framework using NONMEM (ver 7.2). The primary outcome was administration of NAC, which was determined based on a serum paracetamol concentration greater than the nomogram line.ResultThere were 1571 admissions in 1303 patients, with a median age of 27 years (12–96 years) and 1140 (73%) were females. The median dose was 10 g (1–100 g). The paracetamol concentration was above the nomogram line in 337 of 1571 (22%) patients. Patients presenting later (first paracetamol concentration between 7 and 16 h post-overdose) compared to those presenting earlier (4–7 h post-overdose) were more likely to have hepatotoxicity (5.5% vs. 0.4%; p < 0.0001), have a toxic paracetamol concentration (34% vs. 18%; p < 0.0001) and receive NAC (48% vs. 23%; p < 0.0001). SDAC reduced the probability of the paracetamol concentration being above the nomogram. Based on SDAC not being administered there was a 5% probability of requiring NAC at a dose of 6–9 g, a 10% chance of requiring NAC at a dose of 13–16 g, a 50% chance of requiring NAC at a dose of 30–34 g and a 90% chance for needing NAC at 48–50 g.ConclusionReported dose was a good predictor of a toxic paracetamol concentration and SDAC reduced the probability of the concentration being above the nomogram. These predictions may assist in determining which patients could be started on NAC immediately.

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

“…Recommendations on gastric decontamination have not changed since 2015. Fifty grams of activated charcoal should be administered to a cooperative, awake adult if they present within 2 hours of ingestion of a toxic dose (Box 1) of immediate release paracetamol, or within 4 hours of immediate release paracetamol overdoses greater than 30 g . GRADE: Strong; Evidence: Low .…”

Lack of respiratory depression in paracetamol‐codeine combination overdoses

“…A second limitation of the study was that reported codeine ingestion was not confirmed by laboratory drug analysis, although all paracetamol cases were confirmed by paracetamol concentrations. A previous study using the same database of paracetamol overdoses found a strong association between dose and paracetamol concentration . It has been shown in a number of studies that using patient history is reliable in identifying the drug taken and a good estimate of the drug dose ingested .…”

Changing the Management of Paracetamol Poisoning

“…12 Some have suggested it might be possible to model acetylcysteine requirements based on estimated paracetamol dose, but this has yet to be tested in practice. 33 …”