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. Objective. To determine if reported dose predicts the need for N-acetylcysteine (NAC).

Methods: Data 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.

Result: There 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.

Conclusion: Reported 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.

Fig. 1.

Probability of the paracetamol concentration being above the nomogram line versus dose (a) for a 30-year-old female with (dashed line) and without (solid line) SDAC; and (b) for a 30-year- old male (solid line) compared to a 30-year-old female (dashed line).